Role of thyroid hormone in skeletal muscle physiology

in Journal of Endocrinology
View More View Less
  • 1 Institute of Biophysics Carlos Chagas Filho, Laboratory of Translational Endocrinology, Rio de Janeiro, Brazil

Contributor Notes

Free access

Thyroid hormones (TH) are crucial for development, growth, differentiation, metabolism and thermogenesis. Skeletal muscle (SM) contractile function, myogenesis and bioenergetic metabolism are influenced by TH. These effects depend on the presence of the TH transporters MCT8 and MCT10 in the plasma membrane, the expression of TH receptors (THRA or THRB) and hormone availability, which is determined either by the activation of thyroxine (T4) into triiodothyronine (T3) by type 2 iodothyronine deiodinases (D2) or by the inactivation of T4 into reverse T3 by deiodinases type 3 (D3). SM relaxation and contraction rates depend on T3 regulation of myosin expression and energy supplied by substrate oxidation in the mitochondria. The balance between D2 and D3 expression determines TH intracellular levels and thus influences the proliferation and differentiation of satellite cells, indicating an important role of TH in muscle repair and myogenesis. During critical illness, changes in TH levels and in THR and deiodinase expression negatively affect SM function and repair. This review will discuss the influence of TH action on SM contraction, bioenergetics metabolism, myogenesis and repair in health and illness conditions.

Abstract

Thyroid hormones (TH) are crucial for development, growth, differentiation, metabolism and thermogenesis. Skeletal muscle (SM) contractile function, myogenesis and bioenergetic metabolism are influenced by TH. These effects depend on the presence of the TH transporters MCT8 and MCT10 in the plasma membrane, the expression of TH receptors (THRA or THRB) and hormone availability, which is determined either by the activation of thyroxine (T4) into triiodothyronine (T3) by type 2 iodothyronine deiodinases (D2) or by the inactivation of T4 into reverse T3 by deiodinases type 3 (D3). SM relaxation and contraction rates depend on T3 regulation of myosin expression and energy supplied by substrate oxidation in the mitochondria. The balance between D2 and D3 expression determines TH intracellular levels and thus influences the proliferation and differentiation of satellite cells, indicating an important role of TH in muscle repair and myogenesis. During critical illness, changes in TH levels and in THR and deiodinase expression negatively affect SM function and repair. This review will discuss the influence of TH action on SM contraction, bioenergetics metabolism, myogenesis and repair in health and illness conditions.

Introduction

Skeletal muscle (SM) is widely distributed and represents approximately 40% of human body mass (Kim et al. 2016); therefore, any change in the energetic profile of SM has important effects on systemic physiology. Indeed, SM is one of the most important tissues involved in energy expenditure and glucose and lipid homeostasis (Salvatore et al. 2014, Lombardi et al. 2015). In SM, thyroid hormones (TH – thyroxine or T4 and triiodothyronine or T3) participate in contractile function, metabolism, myogenesis and regeneration (Simonides & van Hardeveld 2008, Dentice et al. 2010, Salvatore et al. 2014). Serum TH levels depend on the hypothalamus–pituitary–thyroid (HPT) axis, which, in turn, responds to several changes in homeostasis (Ortiga-Carvalho et al. 2016). In addition to serum levels, specific tissue concentrations of TH in SM depend on local levels of TH transporters, TH receptors and deiodinase activity (Boelen et al. 2017). Therefore, in this review, we aim to discuss the main effects of TH in muscular physiological processes.

Skeletal muscle physiology

SM fibres are classified according to twitch speed and primary ATP production pathway. Figure 1 depicts the main characteristics of fibre types, namely, I, IIa, IIx and IIb. SM presents pure or hybrid fibres composed of combinations of these fibre types that are recruited for different performances according to their individual features. In general, sustained contraction is mediated by type I fibres, which are slow-twitch fibres, whereas type II fibres perform short burst activities and are called fast-twitch fibres (Schiaffino & Reggiani 2011). The SM metabolisms of slow- and fast-twitch fibres are also different. As shown in Fig. 1A, the slow fibres are oxidative and have more mitochondria and myoglobin, whereas fast fibres are more glycolytic and exhibit more glycogen and phosphocreatine. Muscle measurements in the steady state or during developed tension revealed that ATPase activity was higher in fast type IIb fibres than that in IIa and IIx fibres, which all have higher activity than slow type I fibres (Stienen et al. 1996). During muscle contraction, the ATP hydrolysis rate increases in all fibre types proportionally to the ATP production speed of each fibre type, which is higher in fast fibres than in the slow ones. Furthermore, the contraction–relaxation rate depends on the regulation of Ca2+ uptake and release from the sarcoplasmic reticulum. As shown in Fig. 1A, the type I fibres present poorly developed sarcoplasmic reticulum in contrast to the well-developed sarcoplasmic reticulum in type II fibres independently of their mitochondrial content (Schiaffino et al. 1970). Additionally, the sarcoplasmic reticulum Ca2+ ATPase (SERCA) type 1 (SERCA1) is associated with faster Ca2+ storage compared to type 2a (SERA2a), which are expressed in type II and I fibres, respectively (Fig. 1A) (Schiaffino & Reggiani 2011). Besides SERCA expression, myosin heavy chain (MYH), the most abundant motor protein in human and rodent SM, is an important intrinsic factor determinant of muscle twitch (Baldwin & Haddad 2001). Type I fibres express myosin heavy chain 7 (MYH7), type IIa fibres present myosin heavy chain 2 (MYH2), type IIx fibres express myosin heavy chain 1 (MYH1) and type IIb fibres present myosin heavy chain 4 (MYH4) (Schiaffino & Reggiani 2011). It is important to note that during SM development, ageing, exercise training and soluble factor stimulus, such as TH, the fibre type profile can be changed; thus, muscle propriety can be changed as well (Simonides & van Hardeveld 2008, Schiaffino & Reggiani 2011, Salvatore et al. 2014).

Figure 1
Figure 1

Characteristics of the different fibre types of muscle and TH regulation. (A) SM presents hybrid fibre types I, IIa, IIx and IIb, which have particular characteristics. Slow fibre type I presents MHY7, while the rapid fibre type IIa has MYH2, fibre type IIx has MYH1 and fibre type IIb has MYH4. Phosphocreatine content is greater in glycolytic IIa and IIb fibres, whereas type II and IIa fibres are more oxidative and have higher mitochondria content. The presence of myoglobin in the cytoplasm gives the reddish colouration, which is expressive in type I fibres and decreases gradually through IIa and IIx fibres and is absent in IIb fibres. Slow fibres present poorly developed SR in contrast to a well-developed SR in fast fibres. Type I fibres express SERCA2a, and type IIa, IIx and IIb fibres present SERCA1a/b. Slow and fast oxidative muscle fibres present higher expression of GLUT4, and at rest, fast fibres accumulate more glycogen than slow fibres. (B) TH induces the fibre type switch to a faster profile of the contraction–relaxation cycle. THs repress slow type I fibre MYH7 expression and stimulate the rapid type II fibres’ MYH-2, -1, and -4 expression. TH-induced expression of SERCA 1a and 2a increases relaxation. Local conversion of T4 to T3, via D2, promotes increased stability of Slc2a4 (GLUT4) mRNA through polyadenylation, which increases the stability and translocation to the sarcolemma. TH increases oxidative capacity due to an increase in mitochondrial content and its protein activity. These regulations occur by nuclear and mitochondrial genome pathways, mediated by THR and p43, respectively, and also by increased Pgc1a expression. TH stimulates UCP3 expression that uncouples ATP synthesis. Overall, TH increases oxygen consumption and the resting metabolic rate.

Citation: Journal of Endocrinology 236, 1; 10.1530/JOE-16-0611

Thyroid hormone action pathway in skeletal muscle

T3 acts in the SM by its classic pathway based on gene expression regulation through T3 interaction with nuclear TH receptors α and β (THRA and THRB), which interact with TH response elements (TREs) in specific promoter regions (Ortiga-Carvalho et al. 2016). THRs also act as transcription factors independent of the ligand (Ortiga-Carvalho et al. 2015). THRA is the main isoform present in SM (Miyabara et al. 2005, Amorim et al. 2009, Dentice et al. 2010, Milanesi et al. 2016).

TH also triggers short-term effects in SM, such as regulation of the activity of membrane transporters (Cordeiro et al. 2013). T4 rapidly stimulates the activity of the Na,K-ATPase in skeletal myotubes, resulting in an increase in the transmembrane resting potential and the frequency of spontaneously occurring action potentials (Bannett et al. 1984). T3 increases the pH in L6 myoblasts from rat SM culture via phospholipase C and intracellular calcium mobilization (Incerpi et al. 1999, D’Arezzo et al. 2004). T3 modifies the kinase activity of p38 and AMPK, which are important in mitochondrial biogenesis in SM fibres (Irrcher et al. 2008).

TH intracellular availability is a result of TH transport across the plasma membrane and the local activation or inactivation of T4 and T3. TH crosses the plasma membrane by facilitated diffusion, which is mediated by TH transporters. In SM, the primary transporters are the monocarboxylate transporters MCT10 and MCT8, which are found both in humans and rodents (Mebis et al. 2009, Di Cosmo et al. 2013). Di Cosmo and coworkers observed that MCT8KO mice presented the same motor activity as WT mice (Di Cosmo et al. 2013). However, MCT8KO mice had signals of increased TH action, including a decrease in the negatively regulated gene Myh7 and an increase in the positively regulated Mhy1 in the slow-twitch SM soleus (Di Cosmo et al. 2013). Indeed, the SM of MCT8KO mice presented 30% more T3 than that of WT mice. Although, in the MCT8D1KO mouse (Dio1 deleted in the MCT8KO mice), the T3 intracellular concentration dropped, but it did not reach WT levels, suggesting that the systemic iodothyronine deiodinase type 1 (D1) was associated with an increase in intramuscular T3 in MCT8KO mice (Di Cosmo et al. 2013). A mutation in SLCI6A2 (MCT8) in humans causes Allan–Herndon–Dudley syndrome (AHDS) (Brockmann et al. 2005), which is characterized by congenital hypotonia that progresses to spasticity, hypoplasia and generalized muscle weakness (Schwartz & Stevenson 2007).

Furthermore, the activity of iodothyronine deiodinases type 2 (D2) and 3 (D3) contributes to the control of intracellular TH levels. D2 converts T4 to T3, which increases T3 availability and likely its effects as well (Bianco et al. 2002). Nonetheless, D3 converts T4 to reverse T3 (rT3) and T3 to diiodothyronine (T2), decreasing the classical T3 nuclear effects (Bianco et al. 2002). The balance between SM D2 and D3 activity changes intra-muscle T3 levels, thus affecting THR occupancy even if the serum TH levels are unchanged (Ambrosio et al. 2017, Boelen et al. 2017).

D2 is constitutively expressed in rodent and human SM and its activity is higher in slow-twitch muscle than in fast-twitch muscle (Visser et al. 2009, Marsili et al. 2010, Ramadan et al. 2011). Hypothyroidism and cold exposure increase muscle D2 activity in rodents (Marsili et al. 2010, Louzada et al. 2014). In humans, D2 modulation by alterations in circulatory levels of TH is controversial. Analysis of D2 and D3 expression in muscle biopsies of thyroidectomized patients before and after T4 therapy did not show differences in DIO2 activity and DIO3 mRNA expression (Heemstra et al. 2009, Visser et al. 2009). However, short-term fasting decreased circulating T3 and increased SM D2 activity in euthyroid patients (Visser et al. 2009).

Thyroid hormone and skeletal muscle physiology

In the initial stages of postnatal development, different stimuli induce SM maturation, the muscle cell loses polyneuronal innervations, mechanical load to specific muscles increases and TH levels raise simultaneously (Slater 1982, Gambke et al. 1983, Cormery et al. 2005). Both neuronal innervation and increased serum TH trigger the transformation of the muscle fibre profile, such as the loss of embryonic and neonatal myosin and an increase in adult fast or slow myosin genes in specific muscles (Schiaffino et al. 1988, 2015). Hypothyroid rats present a delay in the switch to adult myosin in fast muscle, but not in slow muscle (Gambke et al. 1983, Butler-Browne et al. 1984, di Maso et al. 2000). The postnatal development of slow fibres depends on weight-bearing activity and electrical stimulation, whereas in fast fibres, T3 signalling is crucial, especially for the transition of neonatal fibre to fibre IIb (Gambke et al. 1983, Adams et al. 2000, di Maso et al. 2000, Baldwin & Haddad 2001). Additionally, the denervation of neonatal fast muscle does not impair the switch of neonatal to adult myosin (Gambke et al. 1983). Therefore, physiological levels of TH contribute to the determination of the normal pattern of fibre distributions in each muscle (Mahdavi et al. 1987, Baldwin & Haddad 2001). T3 represses Myh7 expression, myosin from fibre type I, and stimulates Myh2, 1 and 4 expression, myosin from fibres IIa, IIx and IIb, respectively, inducing faster muscle contraction in rats (Fig. 1B) (Larsson et al. 1994). Moreover, T3 stimulates slow-to-fast muscle fibre type conversion by inducing the transition of MYH7 to MYH2, MYH2 to MYH1 and MYH1 to MYH4 (Simonides & van Hardeveld 2008).

In slow- and fast-twitch muscle, the deletion of Thra increased MYH7, while Thrb deletion only had an impact on Myh7 expression in fast-twitch SM (Yu et al. 2000). Additionally, T3 can alter twitch profiles by modulating miRNA expression. miR-133a is induced by T3 and highly expressed in fast-twitch muscle (Zhang et al. 2014). The slow-to-fast transition induced by T3 is impaired by miR-133a repression (Zhang et al. 2014). Additionally, miR-133a-knockout mice have a fast-to-slow SM transition (Liu et al. 2011). Thus, target miRNAs could be an indirect mechanism of T3 action on SM plasticity.

Postnatal sarcoplasmic reticulum development is also dependent on T3, especially the expression of SERCA1 in fast-twitch muscle (Simonides & van Hardeveld 1989, van der Linden et al. 1992). The fast fibre SERCA1 is associated with increased Ca2+ storage, which partly explains the increased speed of the contraction–relaxation cycle. Since this process requires elevated energy, it is not sustained for long periods (Schiaffino & Reggiani 2011). As shown in Fig. 1B, TH accelerates relaxation by T3 direct stimulation of ATP2A1 (SERCA1A) and ATP2A2 (SERCA2A) expression (Hartong et al. 1994, Muller et al. 1994, Simonides et al. 1996).

In 2005, it was postulated that SM could participate in the regulation of serum T3 levels since SM is wildly distributed and has a large mass (Maia et al. 2005). However, global D2KO mice have normal levels of T3 and increased levels of T4 and TSH (Schneider et al. 2001). Moreover, knockdown of muscular D2 by approximately 40–50% during muscle development or after muscle fibre differentiation does not significantly change TH serum levels (Werneck-de-Castro et al. 2015, Ignacio et al. 2017). Although it is important to note that despite normal TH serum levels, D2KO mice present a reduction in SM T3 levels and a hypothyroid muscle phenotype (Schneider et al. 2001, Bárez-López et al. 2014).

Thyroid hormone affects skeletal muscle metabolism

T3 treatment increases maximal oxygen consumption, which is more than two times bigger in the soleus than in the plantaris, which are slow-twitch oxidative fibres and fast-twitch mixed SM, respectively (Bahi et al. 2005). The stimulus for switching from a glycolytic fibre to an oxidative one increases not only mitochondrial content but also mitochondrial fusion, forming elongated mitochondria. As represented in Fig. 1, slow-twitch SM presents more mitochondria than fast-twitch ones (Mishra et al. 2015).

T3 levels promote appropriate muscle responsiveness to insulin, and this effect depends on the conversion of T4 to T3 by local D2 as shown in D2-deficient myotube cultures, which present blunted insulin signalling (Grozovsky et al. 2009). This effect is partly associated with the increase in glucose uptake by TH upregulation of Slc2a4 (GLUT4) in basal and insulin-induced conditions (Weinstein et al. 1994). THR forms a complex with myogenic differentiation 1 (MYOD1) and myocyte enhancer factor 2 (MEF2) on the TRE of the Slc2a4 gene promoter in L6E9 muscle cells and rat SM in vivo, contributing to transcriptional regulation (Fig. 1B) (Torrance et al. 1997, Santalucía et al. 2001). Furthermore, TH promotes rapid post-transcriptional effects on Slc2a4 mRNA polyadenylation, which increases transcript stability and GLUT4 availability and translocation to the sarcolemma in mice (Fig. 1B) (Brunetto et al. 2012). Slow and fast oxidative muscle fibres present a higher expression of GLUT4 and a greater glucose uptake capacity than fast glycolytic fibres (Fig. 1A) (Goodyear et al. 1991, Kong et al. 1994). Thus, hypothyroid mice present decreased glucose uptake induced by insulin. Nonetheless, elevated T3 levels apparently do not further increase glucose uptake capacity, as thyrotoxicosis models present increased gluconeogenesis and reduced insulin action (Schiaffino & Reggiani 2011).

Besides glucose uptake, TH stimulates oxidative pathways by increasing mitochondrial biogenesis. TH-induced mitochondrial biogenesis occurs through stimulation of the expression of intermediate factors, especially the transcription factor peroxisome proliferator-activated receptor coactivator 1α (PGC1A), which is a key regulator of mitochondrial biogenesis in SM (Schnyder & Handschin 2015). T3 positively regulated PGC1A by THR directly on the gene promoter (Fig. 1B) (Wulf et al. 2008). Additionally, D2 activity is important to treadmill exercise-induced PGC1A stimulation and its downstream effects on mitochondrial function of the soleus and gastrocnemius muscles (Bocco et al. 2016). Recently, Lesmana and coworkers demonstrated that TH-induced mitochondrial biogenesis and activity are dependent on T3-induced autophagy (Lesmana et al. 2016). These TH effects on mitochondria were blocked in L6 myotubes lacking the autophagy-related gene 5 (Atg5) by short hairpin RNA (shRNA) lentivirus transformation (Lesmana et al. 2016).

Uncouple protein 2 and 3 (UCP2, UCP3) are members of the mitochondrial carrier family and promote mitochondrial uncoupling in SM, thus dissipating energy in the form of heat and decreasing the energy efficiency of the cell. UCP2 is widely distributed, and UCP3 is primarily expressed in SM (Gong et al. 1997, Solmonson & Mills 2016). It was suggested that TH could increase resting metabolic rate (RMR) through modulations in UCP3. The SM mitochondria of UCP3-deficient mice are more coupled and produce more reactive oxygen species (ROS) (Gong et al. 2000, Vidal-Puig et al. 2000), whereas the opposite effect was observed in mice overexpressing human UCP3 (Clapham et al. 2000). T3 also increases the expression of citrate synthase, which performs the first step of the citric acid cycle (Bahi et al. 2005) and stimulates glycerol-3-phosphate dehydrogenase, a key enzyme of intermediary metabolism (Dümmler et al. 1996). Furthermore, TH also stimulates oxidative phosphorylation in male rats due to the increased activity of cytochrome c oxidase 1 and 4 (COX1 and COX4, respectively), the last enzymes in the electron transport chain of mitochondria (Bahi et al. 2005). Additionally, healthy young men treated with T3 for 14 days demonstrated an increase in RMR, UCP3 and UCP2 and a decrease in respiratory quotient, but did not show an increase COX4 or in nuclear respiratory factor 1 (NRF1) mRNA expression (Barbe et al. 2001). However, it is unknown whether there is a relationship between the substrate used and the TH levels. Therefore, the mechanism associated with T3 increased SM mitochondrial activity, and oxygen consumption is related to the stimulation of mitochondrial enzymes and UCP3 (Barbe et al. 2001, de Lange et al. 2001, Bahi et al. 2005).

Analysis of patient samples presenting with the classical form of resistance to TH (RTH-THRB mutation) demonstrated an increase in RMR compared to healthy individuals (Mitchell et al. 2010). This increased RMR was due to the action of THRA in the muscle, which was responding to the TH excess seen in those patients. When the authors measured muscle substrate oxidation, they found an increased rate (75%) of tricarboxylic acid (TCA) cycle flux and decreased rates of ATP synthase flux, thus decreasing muscle mitochondrial energy uncoupling (ratio of TCA/ATP). Furthermore, the intramyocellular lipid content increased in the soleus muscle of RTH subjects compared to the control (Mitchell et al. 2010).

Studying a mouse model of Thra deletion, it was observed that these animals preferentially use fat as fuel due to an increase in the expression of lipoprotein lipase in SM, and these mice present an increase in food consumption together with a leaner profile compared to WT mice (Pelletier et al. 2008). Moreover, Thra-0/0 mice present increased levels of SM D2, which are associated with an increase in fat oxidation in this tissue (Ramadan et al. 2011).

Overall, independent of the metabolized substrate, TH induces increased mitochondrial activity, oxidative phosphorylation and oxygen consumption through the stimulation of mitochondrial enzymes and UCP3 (Fig. 1B) (de Lange et al. 2001, Bahi et al. 2005).

Thyroid hormone impact on myogenesis

SM function depends on energy turnover, contraction and relaxation rates and on muscle tissue regeneration. SM growth and regeneration are dependent on the proliferation and differentiation of the muscle stem cell population, satellite cells (SC), in a process known as myogenesis. SC niches are located between the muscle fibre sarcolemma and the basal lamina, which are normally close to the endothelial area (Fig. 2) (Christov et al. 2007). The muscle stem cell niche location permits SCs to receive extrinsic signals from the bloodstream and intrinsic signals from the muscle fibres. Both stimuli can modulate the proliferation and differentiation of progenitor cells (Beermann et al. 1983, Linker et al. 2003, Bentzinger et al. 2012). The myogenic process is summarized in Fig. 2.

Figure 2
Figure 2

Myogenesis and TH. The SC niches are next to blood vessels, between the basal lamina and the myofiber. Pax7 and Foxo3 are expressed by quiescent SCs, and these factors are involved in cell survival and self-renewal. Under the appropriate stimulus, SCs enter the differentiation pathway and thus turn into committed SCs expressing PAX7 and D3. The low intracellular T3 favors the survival and cell proliferation. The activated SCs express PAX7 and MYF5 and decrease the expression of D3; thus, intracellular T3 can increase and induce the expression of FOXO3, which induces the expression of D2 and represses D3. Both T3 and FOXO3 induce MYOD1 leading to the progression of the differentiation of activated SC into the proliferative myoblast. In these, THRA1 represses MYOD1 and myogenin expression, whereas MYOD1 induces Thra1 expression. Additionally, FOXO3 induces D2 expression, leading to an increase in intracellular T3, which represses AP1 and induces the expression of MYOD1 and myogenin. T3, MYF4 and myogenin are involved in the terminal differentiation of myocytes into myotubes/myofibers, and these factors stimulate the expression of MYH and SERCA.

Citation: Journal of Endocrinology 236, 1; 10.1530/JOE-16-0611

Myogenesis is controlled by a hierarchical expression of transcription factors that is dependent on environmental conditions and the differentiation state of the cell (Bentzinger et al. 2012, Dumont et al. 2015b). Pax7 regulates the expression of the myogenic regulatory factors (MRF), a family of transcription factors that are essential to the progression of myogenesis, such as myogenic factor 5 (MYF5) and MYOD1 (Oustanina et al. 2004, Relaix et al. 2006, Collins et al. 2009, Bentzinger et al. 2012, Dumont et al. 2015b). They have redundant roles in myogenesis and induce myogenin (MYOG) and MRF4 expression by myoblasts (Dumont et al. 2015a). MYOD1 and MYOG are involved in terminal myogenic differentiation and are positively regulated by T3 (Fig. 2) (Carnac et al. 1992, Downes et al. 1993). MYOD1 expression after muscle injury is similar between euthyroid and hypothyroid mice; however, the SC from hyperthyroid regenerative sites express more MYOD1 (Anderson et al. 1998).

The control of intracellular T3 levels is fundamental to myogenesis progression (Ambrosio et al. 2017). Dio3 expression is one of the controllers of proliferation and survival signalling in SCs (Dentice et al. 2014, Ambrosio et al. 2017). D3 is highly expressed in activated and proliferating SCs; however, it is downregulated during the differentiation process (Fig. 2) (Dentice et al. 2014). D3 ablation induces committed SC apoptosis, as T3 activates the FOXO3 and MYOD1 pro-apoptotic axis (Fig. 2) (Dentice et al. 2014, Ambrosio et al. 2017). Foxo3 expression is also important in SC self-renewal, as it is associated with the return of SC quiescence after cell division (Mammucari et al. 2007). As indicated in Fig. 2, D3 expression is downregulated during the differentiation process, and D2 is upregulated. These changes in expression lead to alterations in intracellular TH levels, which are required for myogenesis progression, suggesting that intracellular T3 should be maintained at a low level only in the beginning of the myogenic process (Dentice et al. 2010, 2014). This suggestion is reinforced by D2KO myogenesis data; these mice had impaired muscle development after birth and reduced regeneration (Dentice et al. 2010). However, downregulation of muscular D2 in adult mice did not impair muscle function or T3 signalling (Werneck-de-Castro et al. 2015). Furthermore, T3 stimulation of myoblast differentiation involves the inhibition of AP1, an inhibitor of differentiation, via THRa (Fig. 2) (Cassar-Malek et al. 1996).

During the myoblast proliferative phase, THRA1 represses MYOD1 and MYOG transcriptional activity independently of T3 presence (Daury et al. 2001); however, MYOD1 induces the transcriptional activity of THRA1, inducing a negative feedback loop in MYOD1 activity as demonstrated in Fig. 2 (Busson et al. 2006). Recently, Milanesi and coworkers used a genetic approach to show that THRA is essential to the proliferation and differentiation of myoblasts by activating the Wnt/beta-catenin signalling pathway (Milanesi et al. 2016). T3 administration to primary avian myoblast cell culture reduced the proliferation rate and increased the myotube fusion index three days after myogenic differentiation induction (Marchal et al. 1993).

An increase in intracellular T3 levels is important to myocyte terminal differentiation, whereas T3 positively regulates Myod1 and Myog expression (Fig. 2, myocytes and myotube panel) (Ambrosio et al. 2017). Additionally, T3, MYOG and MYF4 effects are crucial for the terminal differentiation of myotubes, inducing the expression of MYH and SERCA (Marsili et al. 2010, Schiaffino & Reggiani 2011, Ambrosio et al. 2017). Thus, as summarized in Fig. 2, low intracellular T3 levels are important to supporting initial SC proliferation, whereas an increase in intracellular TH responsiveness is associated with SM terminal differentiation.

Influence of illness on skeletal muscle thyroid hormone signalling

Critical illness induces changes in the hypothalamic–anterior–pituitary–peripheral–hormonal axis, including decreased plasma TH levels with no significant increase in TSH (Van den Berghe 2016). This condition is known as ‘non-thyroid illness syndrome’ (NTIS). Acute and critical illnesses also induce changes in TH metabolism, including alterations in SM responsiveness to TH (Fliers et al. 2014). Deiodinase, THR and TH transporter expression are modulated in SM during acute, chronic and systemic inflammation (Boelen et al. 2011, Bloise et al. 2016, Van den Berghe 2016). These changes affect TH responsiveness and can lead to altered muscle function.

During NTIS, the plasma levels of pro-inflammatory cytokines are increased. These cytokines exert their action via the NFκB, ERK1/2 and AP1 signal transduction pathways. NFκB and AP1 response elements have been characterized in the D2 promoter (Gereben & Salvatore 2005, Zeold et al. 2006), suggesting that activation of these pathways affects D2 expression. However, the NFκB pathway does not seem to be involved in the regulation of muscle D2 expression during illness in mice (Kwakkel et al. 2009). Not much is known about the mechanism involved in muscle D3 regulation during inflammation. Although D3 can be stimulated via the ERK1/2 and p38 signalling pathways in human non-muscular cells, little is known about these effects in SM (Pallud et al. 1999, Wajner et al. 2011).

It has been shown that muscle D2 mRNA and activity are increased in patients with prolonged critical illness compared to healthy controls (Mebis et al. 2006). Nevertheless, septic patients had decreased SM DIO2 expression, whereas muscle DIO3 expression increased (Rodriguez-Perez et al. 2008). In this sense, murine severe Streptococcus pneumoniae infection decreased limb muscle and diaphragm Dio2 expression, whereas Dio3 remained unchanged in limb muscle, but increased in the diaphragm (Kwakkel et al. 2009, Bloise et al. 2016). Furthermore, acute inflammation induces an increase in Dio2 and a decrease in Dio3 expression in hind limb (Kwakkel et al. 2009, Boelen et al. 2017). Taken together, in sepsis and acute inflammation, there is a decrease in muscle D2; thus, it could lead to a decrease in the local conversion of T4 to T3. Meanwhile, chronic aseptic inflammation induces the expression of D2 and D3 in limb muscle (Kwakkel et al. 2009), probably leading to an increase in intracellular T2. However, Dio3 expression decreased and Dio2 expression did not significantly change in the diaphragm of mice under chronic aseptic inflammation (Bloise et al. 2016). Conversely, intramuscular T4 and T3 decrease in different NTIS models, lipopolysaccharide (LPS) induction of acute inflammation, chronic aseptic inflammation and bacterial sepsis (Boelen et al. 2017). Additionally, SM from acute inflammation challenged mice decrease expression of the T3-positively regulated gene Myog; however, in the chronic model, it was observed to increase (Boelen et al. 2017). These data suggest that muscle response is dependent on the type of inflammatory stimulus and could be different according to the SM type and/or function.

Sepsis and chronic inflammation mouse models decrease hind limb muscle Thra expression, whereas Thra is increased in the diaphragm during chronic inflammation (Kwakkel et al. 2009, 2010, Bloise et al. 2016, Boelen et al. 2017). During acute inflammation, the decrease in muscle expression of Dio3 is dependent on Thra; however, Dio2 upregulation is not impacted by Thra in mouse limb muscle (Kwakkel et al. 2009). SLCI6A2 (MCT8) is upregulated in SM biopsies from critically ill patients in the intensive care unit (ICU) compared to acute surgical stressed biopsies (Mebis et al. 2009). Furthermore, muscle SLCI6A2 expression was inversely correlated to serum TH concentrations in these patients (Mebis et al. 2009). Because the low free T4 levels are associated with the severity of the disease (Van den Berghe 2016), these data suggest that the sickest patients would have an increase in MCT8 expression in muscle cells. Meanwhile, murine diaphragm Slci6a2 expression decreases during sepsis; however, chronic inflammation did not change its expression (Bloise et al. 2016). In addition, hind limb Slci6a2 expression did not change during acute or chronic inflammation, although it decreased during bacterial sepsis (Boelen et al. 2017). Thus, during critical illness, TH transport increases in association with the severity of the disease in humans and decreases in NTIS mouse models. Taking together, the murine and patient data, MCT8 expression is differently regulated by the type of inflammation, which contributes to changes in TH transport across the plasma membrane.

Critical illnesses frequently lead to diaphragm muscle dysfunction. Thus, these patients need mechanical ventilation and are sent to the ICU. After ICU discharge, patients can present muscle weakness and fatigue even 12 months after recovery from the initial disease (Herridge et al. 2003). The loss of muscle strength and increase in fatigue are associated with decreased mitochondrial function in critically ill patients (Fredriksson et al. 2005, 2006). Interestingly, septic patients have decreased mitochondrial content in both leg and respiratory muscles; however, this decrease minimally impacts energy production in respiratory muscle (Fredriksson et al. 2006, Fredriksson & Rooyackers 2007). Additionally, SM dysfunction is associated with decreased mitochondrial bioenergetics in septic mice (Zolfaghari et al. 2015). LPS administration to C2C12 myotubes was used as an inflammatory infection model to investigate the role of inflammation on muscular mitochondrial function. LPS induces a decrease in muscle mitochondrial function in vitro, which is at least partly dependent on the decrease in Dio2 expression (Bloise et al. 2016).

A reduction of serum TH levels during illness is postulated as a physiological adaptation to reduce energy requirements during acute illness (Fliers et al. 2015). SM is the primary organ responsible for glucose uptake in response to insulin and in high energy-demanding conditions, such as disease. In these situations, muscular protein catabolism can be stimulated to maintain an energy supply to other organs (Argilés et al. 2016). Therefore, reducing the anabolic response mediated by TH in SM could favour energy conservation during illness. Thus, NTIS would be an adaptation to save energy (Van den Berghe 2016). However, during prolonged illness, low levels of TH could be deleterious and may require clinical intervention. The muscle wasting observed in ICU patients could be associated with decreased TH signalling. Taken together, deiodinase, transporters and THR data suggest that the type and duration of an inflammatory response lead to different patterns of SM TH responsiveness. Additionally, SM type is also differently modulated by inflammation.

Conclusions

TH are key regulators of the development, regeneration and metabolism of SM. T3 stimulates the expression of MYH characteristic of fast-twitch fibres, increases mitochondrial biogenesis and the relaxation–contraction rate. During myogenesis, the intracellular T3 concentration is precisely regulated by D2 and D3, which is crucial for the progression of muscle progenitor cell differentiation. Additionally, illness influences SM function through the regulation of TH responsiveness in this tissue. Therefore, TH influences diverse aspects of muscle physiology by different mechanisms. Thus, the field still needs further studies to bring new insights on the pathophysiology of SM under TH action.

Declaration of interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of this review.

Funding

This work was supported by grants from the Brazilian Endocrine and Metabolism Society – Thyroid department (SBEM), CAPES, CNPq and FAPERJ Foundation (Brazil).

Acknowledgements

The authors would like to thank Thiago Ladeira for designing the figures.

References

  • Adams GR, Haddad F & Baldwin KM 2000 The interaction of space flight and thyroid state on somatic and skeletal muscle growth and myosin heavy chain expression on neonatal rodents. Journal of Gravitational Physiology 7 P15P18.

    • Search Google Scholar
    • Export Citation
  • Ambrosio R, De Stefano MA, Di Girolamo D & Salvatore D 2017 Thyroid hormone signaling and deiodinase actions in muscle stem/progenitor cells. Molecular and Cellular Endocrinology [epub]. (https://doi.org/10.1016/j.mce.2017.06.014)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Amorim BS, Ueta CB, Freitas BC, Nassif RJ, Gouveia CH, Christoffolete MA, Moriscot AS, Lancelloti CL, Llimona F & Barbeiro HV et al. 2009 A TRbeta-selective agonist confers resistance to diet-induced obesity. Journal of Endocrinology 203 291299. (https://doi.org/10.1677/JOE-08-0539)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Anderson JE, McIntosh LM, Moor AN & Yablonka-Reuveni Z 1998 Levels of MyoD protein expression following injury of mdx and normal limb muscle are modified by thyroid hormone. Journal of Histochemistry and Cytochemistry 46 5967. (https://doi.org/10.1177/002215549804600108)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Argilés JM, Campos N, Lopez-Pedrosa JM, Rueda R & Rodriguez-Mañas L 2016 Skeletal muscle regulates metabolism via interorgan crosstalk: roles in health and disease. Journal of the American Medical Directors Association 17 789796. (https://doi.org/10.1016/j.jamda.2016.04.019)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bahi L, Garnier A, Fortin D, Serrurier B, Veksler V, Bigard AX & Ventura-Clapier R 2005 Differential effects of thyroid hormones on energy metabolism of rat slow- and fast-twitch muscles. Journal of Cellular Physiology 203 589598. (https://doi.org/10.1002/jcp.20273)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Baldwin KM & Haddad F 2001 Effects of different activity and inactivity paradigms on myosin heavy chain gene expression in striated muscle. Journal of Applied Physiology 90 345357.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Bannett RR, Sampson SR & Shainberg A 1984 Influence of thyroid hormone on some electrophysiological properties of developing rat skeletal muscle cells in culture. Brain Research 294 7582. (https://doi.org/10.1016/0006-8993(84)91311-8)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Barbe P, Larrouy D, Boulanger C, Chevillotte E, Viguerie N, Thalamas C, Oliva Trastoy M, Roques M, Vidal H & Langin D 2001 Triiodothyronine-mediated up-regulation of UCP2 and UCP3 mRNA expression in human skeletal muscle without coordinated induction of mitochondrial respiratory chain genes. FASEB Journal 15 1315. (https://doi.org/10.1096/fj.00-0502fje)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Bárez-López S, Bosch-García D, Gómez-Andrés D, Pulido-Valdeolivas I, Montero-Pedrazuela A, Obregon MJ & Guadaño-Ferraz A 2014 Abnormal motor phenotype at adult stages in mice lacking type 2 deiodinase. PLoS ONE 9 e103857. (https://doi.org/10.1371/journal.pone.0103857)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Beermann DH, Hood LF & Liboff M 1983 Satellite cell and myonuclei populations in rat soleus and extensor digitorum longus muscles after maternal nutritional deprivation and realimentation. Journal of Animal Science 57 16181625. (https://doi.org/10.2527/jas1983.5761618x)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bentzinger CF, Wang YX & Rudnicki MA 2012 Building muscle: molecular regulation of myogenesis. Cold Spring Harbor Perspectives in Biology 4 a008342. (https://doi.org/10.1101/cshperspect.a008342)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bianco AC, Salvatore D, Gereben B, Berry MJ & Larsen PR 2002 Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases. Endocrine Reviews 23 3889. (https://doi.org/10.1210/edrv.23.1.0455)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bloise FF, van der Spek AH, Surovtseva OV, Ortiga-Carvalho TM, Fliers E & Boelen A 2016 Differential effects of sepsis and chronic inflammation on diaphragm muscle fiber type, thyroid hormone metabolism, and mitochondrial function. Thyroid 26 600609. (https://doi.org/10.1089/thy.2015.0536)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bocco BM, Louzada RA, Silvestre DH, Santos MC, Anne-Palmer E, Rangel IF, Abdalla S, Ferreira AC, Ribeiro MO & Gereben B et al. 2016 Thyroid hormone activation by type 2 deiodinase mediates exercise-induced peroxisome proliferator-activated receptor-γ coactivator-1α expression in skeletal muscle. Journal of Physiology 594 52555269. (https://doi.org/10.1113/JP272440)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Boelen A, Kwakkel J & Fliers E 2011 Beyond low plasma T3: local thyroid hormone metabolism during inflammation and infection. Endocrine Reviews 32 670693. (https://doi.org/10.1210/er.2011-0007)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Boelen A, van der Spek AH, Bloise F, de Vries EM, Surovtseva OV, van Beeren M, Ackermans MT, Kwakkel J & Fliers E 2017 Tissue thyroid hormone metabolism is differentially regulated during illness in mice. Journal of Endocrinology 233 2536. (https://doi.org/10.1530/JOE-16-0483)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Brockmann K, Dumitrescu AM, Best TT, Hanefeld F & Refetoff S 2005 X-linked paroxysmal dyskinesia and severe global retardation caused by defective MCT8 gene. Journal of Neurology 252 663666. (https://doi.org/10.1007/s00415-005-0713-3)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Brunetto EL, Teixeira SAS, Giannocco G, Machado UF & Nunes MT 2012 T3 rapidly increases SLC2A4 gene expression and GLUT4 trafficking to the plasma membrane in skeletal muscle of rat and improves glucose homeostasis. Thyroid 22 7079. (https://doi.org/10.1089/thy.2010.0409)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Busson M, Daury L, Seyer P, Grandemange S, Pessemesse L, Casas F, Wrutniak-Cabello C & Cabello G 2006 Avian MyoD and c-Jun coordinately induce transcriptional activity of the 3,5,3′-triiodothyronine nuclear receptor c-ErbAalpha1 in proliferating myoblasts. Endocrinology 147 34083418. (https://doi.org/10.1210/en.2006-0101)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Butler-Browne GS, Herlicoviez D & Whalen RG 1984 Effects of hypothyroidism on myosin isozyme transitions in developing rat muscle. FEBS Letters 166 7175. (https://doi.org/10.1016/0014-5793(84)80047-2)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Carnac G, Albagli-Curiel O, Vandromme M, Pinset C, Montarras D, Laudet V & Bonnieu A 1992 3,5,3′-Triiodothyronine positively regulates both MyoD1 gene transcription and terminal differentiation in C2 myoblasts. Molecular Endocrinology 6 11851194. (https://doi.org/10.1210/mend.6.8.1406697)

    • Search Google Scholar
    • Export Citation
  • Cassar-Malek I, Marchal S, Rochard P, Casas F, Wrutniak C, Samarut J & Cabello G 1996 Induction of c-Erb A-AP-1 interactions and c-Erb A transcriptional activity in myoblasts by RXR. Consequences for muscle differentiation. Journal of Biological Chemistry 271 1139211399. (https://doi.org/10.1074/jbc.271.19.11392)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Christov C, Chrétien F, Abou-Khalil R, Bassez G, Vallet G, Authier FJ, Bassaglia Y, Shinin V, Tajbakhsh S & Chazaud B et al. 2007 Muscle satellite cells and endothelial cells: close neighbors and privileged partners. Molecular Biology of the Cell 18 13971409. (https://doi.org/10.1091/mbc.E06-08-0693)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Clapham JC, Arch JR, Chapman H, Haynes A, Lister C, Moore GB, Piercy V, Carter SA, Lehner I & Smith SA et al. 2000 Mice overexpressing human uncoupling protein-3 in skeletal muscle are hyperphagic and lean. Nature 406 415418. (https://doi.org/10.1038/35019082)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Collins CA, Gnocchi VF, White RB, Boldrin L, Perez-Ruiz A, Relaix F, Morgan JE & Zammit PS 2009 Integrated functions of Pax3 and Pax7 in the regulation of proliferation, cell size and myogenic differentiation. PLoS ONE 4 e4475. (https://doi.org/10.1371/journal.pone.0004475)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Cordeiro A, Souza LL, Einicker-Lamas M & Pazos-Moura CC 2013 Non-classic thyroid hormone signalling involved in hepatic lipid metabolism. Journal of Endocrinology 216 R47R57. (https://doi.org/10.1530/JOE-12-0542)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Cormery B, Beaumont E, Csukly K & Gardiner P 2005 Hindlimb unweighting for 2 weeks alters physiological properties of rat hindlimb motoneurones. Journal of Physiology 568 841850. (https://doi.org/10.1113/jphysiol.2005.091835)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • D’Arezzo S, Incerpi S, Davis FB, Acconcia F, Marino M, Farias RN & Davis PJ 2004 Rapid nongenomic effects of 3,5,3′-triiodo-L-thyronine on the intracellular pH of L-6 myoblasts are mediated by intracellular calcium mobilization and kinase pathways. Endocrinology 145 56945703. (https://doi.org/10.1210/en.2004-0890)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Daury L, Busson M, Casas F, Cassar-Malek I, Wrutniak-Cabello C & Cabello G 2001 The triiodothyronine nuclear receptor c-ErbAalpha1 inhibits avian MyoD transcriptional activity in myoblasts. FEBS Letters 508 236240. (https://doi.org/10.1016/S0014-5793(01)03063-0)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • de Lange P, Lanni A, Beneduce L, Moreno M, Lombardi A, Silvestri E & Goglia F 2001 Uncoupling protein-3 is a molecular determinant for the regulation of resting metabolic rate by thyroid hormone. Endocrinology 142 34143420. (https://doi.org/10.1210/endo.142.8.8303)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Dentice M, Marsili A, Ambrosio R, Guardiola O, Sibilio A, Paik JH, Minchiotti G, DePinho RA, Fenzi G & Larsen PR et al. 2010 The FoxO3/type 2 deiodinase pathway is required for normal mouse myogenesis and muscle regeneration. Journal of Clinical Investigation 120 40214030. (https://doi.org/10.1172/JCI43670)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Dentice M, Ambrosio R, Damiano V, Sibilio A, Luongo C, Guardiola O, Yennek S, Zordan P, Minchiotti G & Colao A et al. 2014 Intracellular inactivation of thyroid hormone is a survival mechanism for muscle stem cell proliferation and lineage progression. Cell Metabolism 20 10381048. (https://doi.org/10.1016/j.cmet.2014.10.009)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Di Cosmo C, Liao XH, Ye H, Ferrara AM, Weiss RE, Refetoff S & Dumitrescu AM 2013 Mct8-deficient mice have increased energy expenditure and reduced fat mass that is abrogated by normalization of serum T3 levels. Endocrinology 154 48854895. (https://doi.org/10.1210/en.2013-1150)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • di Maso NA, Caiozzo VJ & Baldwin KM 2000 Single-fiber myosin heavy chain polymorphism during postnatal development: modulation by hypothyroidism. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology 278 R1099R1106.

    • Search Google Scholar
    • Export Citation
  • Downes M, Griggs R, Atkins A, Olson EN & Muscat GE 1993 Identification of a thyroid hormone response element in the mouse myogenin gene: characterization of the thyroid hormone and retinoid X receptor heterodimeric binding site. Cell Growth and Differentiation 4 901909.

    • Search Google Scholar
    • Export Citation
  • Dumont NA, Bentzinger CF, Sincennes MC & Rudnicki MA 2015a Satellite cells and skeletal muscle regeneration. Comprehensive Physiology 5 10271059. (https://doi.org/10.1002/cphy.c140068)

    • Search Google Scholar
    • Export Citation
  • Dümmler K, Müller S & Seitz HJ 1996 Regulation of adenine nucleotide translocase and glycerol 3-phosphate dehydrogenase expression by thyroid hormones in different rat tissues. Biochemical Journal 317 913918.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Dumont NA, Wang YX & Rudnicki MA 2015b Intrinsic and extrinsic mechanisms regulating satellite cell function. Development 142 15721581. (https://doi.org/10.1242/dev.114223)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Fliers E, Kalsbeek A & Boelen A 2014 Beyond the fixed setpoint of the hypothalamus-pituitary-thyroid axis. European Journal of Endocrinology 171 R197R208. (https://doi.org/10.1530/EJE-14-0285)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Fliers E, Bianco AC, Langouche L & Boelen A 2015 Thyroid function in critically ill patients. Lancet Diabetes and Endocrinology 3 816825. (https://doi.org/10.1016/S2213-8587(15)00225-9)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Fredriksson K & Rooyackers O 2007 Mitochondrial function in sepsis: respiratory versus leg muscle. Critical Care Medicine 35 S449S453. (https://doi.org/10.1097/01.CCM.0000278048.00896.4B)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Fredriksson K, Radell P, Eriksson LI, Hultenby K & Rooyackers O 2005 Effect of prolonged mechanical ventilation on diaphragm muscle mitochondria in piglets. Acta Anaesthesiologica Scandinavica 49 11011107. (https://doi.org/10.1111/j.1399-6576.2005.00718.x)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Fredriksson K, Hammarqvist F, Strigard K, Hultenby K, Ljungqvist O, Wernerman J & Rooyackers O 2006 Derangements in mitochondrial metabolism in intercostal and leg muscle of critically ill patients with sepsis-induced multiple organ failure. American Journal of Physiology: Endocrinology and Metabolism 291 E1044E1050. (https://doi.org/10.1152/ajpendo.00218.2006)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Gambke B, Lyons GE, Haselgrove J, Kelly AM & Rubinstein NA 1983 Thyroidal and neural control of myosin transitions during development of rat fast and slow muscles. FEBS Letters 156 335339. (https://doi.org/10.1016/0014-5793(83)80524-9)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Gereben B & Salvatore D 2005 Pretranslational regulation of type 2 deiodinase. Thyroid 15 855864. (https://doi.org/10.1089/thy.2005.15.855)

  • Gong DW, He Y, Karas M & Reitman M 1997 Uncoupling protein-3 is a mediator of thermogenesis regulated by thyroid hormone, beta3-adrenergic agonists, and leptin. Journal of Biological Chemistry 272 2412924132. (https://doi.org/10.1074/jbc.272.39.24129)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Gong DW, Monemdjou S, Gavrilova O, Leon LR, Marcus-Samuels B, Chou CJ, Everett C, Kozak LP, Li C & Deng C et al. 2000 Lack of obesity and normal response to fasting and thyroid hormone in mice lacking uncoupling protein-3. Journal of Biological Chemistry 275 1625116257. (https://doi.org/10.1074/jbc.M910177199)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Goodyear LJ, Hirshman MF, Smith RJ & Horton ES 1991 Glucose transporter number, activity, and isoform content in plasma membranes of red and white skeletal muscle. American Journal of Physiology 261 E556E561.

    • Search Google Scholar
    • Export Citation
  • Grozovsky R, Ribich S, Rosene ML, Mulcahey MA, Huang SA, Patti ME, Bianco AC & Kim BW 2009 Type 2 deiodinase expression is induced by peroxisomal proliferator-activated receptor-gamma agonists in skeletal myocytes. Endocrinology 150 19761983. (https://doi.org/10.1210/en.2008-0938)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hartong R, Wang N, Kurokawa R, Lazar MA, Glass CK, Apriletti JW & Dillmann WH 1994 Delineation of three different thyroid hormone-response elements in promoter of rat sarcoplasmic reticulum Ca2+ATPase gene. Demonstration that retinoid X receptor binds 5′ to thyroid hormone receptor in response element 1. Journal of Biological Chemistry 269 1302113029.

    • Search Google Scholar
    • Export Citation
  • Heemstra KA, Soeters MR, Fliers E, Serlie MJ, Burggraaf J, van Doorn MB, van der Klaauw AA, Romijn JA, Smit JW & Corssmit EP et al. 2009 Type 2 iodothyronine deiodinase in skeletal muscle: effects of hypothyroidism and fasting. Journal of Clinical Endocrinology and Metabolism 94 21442150. (https://doi.org/10.1210/jc.2008-2520)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Herridge MS, Cheung AM, Tansey CM, Matte-Martyn A, Diaz-Granados N, Al-Saidi F, Cooper AB, Guest CB, Mazer CD & Mehta S et al. 2003 One-year outcomes in survivors of the acute respiratory distress syndrome. New England Journal of Medicine 348 683693. (https://doi.org/10.1056/NEJMoa022450)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Ignacio DL, Silvestre DH, Anne-Palmer E, Bocco BM, Fonseca TL, Ribeiro MO, Gereben B, Bianco AC & Werneck-de-Castro JP 2017 Early developmental disruption of type 2 deiodinase pathway in mouse skeletal muscle does not impair muscle function. Thyroid 27 577586. (https://doi.org/10.1089/thy.2016.0392)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Incerpi S, Luly P, De Vito P & Farias RN 1999 Short-term effects of thyroid hormones on the Na/H antiport in L-6 myoblasts: high molecular specificity for 3,3′,5-triiodo-L-thyronine. Endocrinology 140 683689. (https://doi.org/10.1210/endo.140.2.6535)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Irrcher I, Walkinshaw DR, Sheehan TE & Hood DA 2008 Thyroid hormone (T3) rapidly activates p38 and AMPK in skeletal muscle in vivo. Journal of Applied Physiology 104 178185. (https://doi.org/10.1152/japplphysiol.00643.2007)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Kim KM, Jang HC & Lim S 2016 Differences among skeletal muscle mass indices derived from height-, weight-, and body mass index-adjusted models in assessing sarcopenia. Korean Journal of Internal Medicine 31 643650. (https://doi.org/10.3904/kjim.2016.015)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Kong X, Manchester J, Salmons S & Lawrence JC 1994 Glucose transporters in single skeletal muscle fibers. Relationship to hexokinase and regulation by contractile activity. Journal of Biological Chemistry 269 1296312967.

    • Search Google Scholar
    • Export Citation
  • Kwakkel J, van Beeren HC, Ackermans MT, Platvoet-Ter Schiphorst MC, Fliers E, Wiersinga WM & Boelen A 2009 Skeletal muscle deiodinase type 2 regulation during illness in mice. Journal of Endocrinology 203 263270. (https://doi.org/10.1677/JOE-09-0118)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Kwakkel J, Chassande O, van Beeren HC, Fliers E, Wiersinga WM & Boelen A 2010 Thyroid hormone receptor {alpha} modulates lipopolysaccharide-induced changes in peripheral thyroid hormone metabolism. Endocrinology 151 19591969. (https://doi.org/10.1210/en.2009-1049)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Larsson L, Li X, Teresi A & Salviati G 1994 Effects of thyroid hormone on fast- and slow-twitch skeletal muscles in young and old rats. Journal of Physiology 481 149161. (https://doi.org/10.1113/jphysiol.1994.sp020426)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Lesmana R, Sinha RA, Singh BK, Zhou J, Ohba K, Wu Y, Yau WW, Bay BH & Yen PM 2016 Thyroid hormone stimulation of autophagy is essential for mitochondrial biogenesis and activity in skeletal muscle. Endocrinology 157 2338. (https://doi.org/10.1210/en.2015-1632)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Linker C, Lesbros C, Stark MR & Marcelle C 2003 Intrinsic signals regulate the initial steps of myogenesis in vertebrates. Development 130 47974807. (https://doi.org/10.1242/dev.00688)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Liu N, Bezprozvannaya S, Shelton JM, Frisard MI, Hulver MW, McMillan RP, Wu Y, Voelker KA, Grange RW & Richardson JA et al. 2011 Mice lacking microRNA 133a develop dynamin 2-dependent centronuclear myopathy. Journal of Clinical Investigation 121 32583268. (https://doi.org/10.1172/JCI46267)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Lombardi A, Moreno M, de Lange P, Iossa S, Busiello RA & Goglia F 2015 Regulation of skeletal muscle mitochondrial activity by thyroid hormones: focus on the ‘old’ triiodothyronine and the ‘emerging’ 3,5-diiodothyronine. Frontiers in Physiology 6 237.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Louzada RA, Santos MC, Cavalcanti-de-Albuquerque JP, Rangel IF, Ferreira AC, Galina A, Werneck-de-Castro JP & Carvalho DP 2014 Type 2 iodothyronine deiodinase is upregulated in rat slow- and fast-twitch skeletal muscle during cold exposure. American Journal of Physiology: Endocrinology and Metabolism 307 E1020E1029. (https://doi.org/10.1152/ajpendo.00637.2013)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Mahdavi V, Izumo S & Nadal-Ginard B 1987 Developmental and hormonal regulation of sarcomeric myosin heavy chain gene family. Circulation Research 60 804814. (https://doi.org/10.1161/01.RES.60.6.804)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Maia AL, Kim BW, Huang SA, Harney JW & Larsen PR 2005 Type 2 iodothyronine deiodinase is the major source of plasma T3 in euthyroid humans. Journal of Clinical Investigation 115 25242533. (https://doi.org/10.1172/JCI25083)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Mammucari C, Milan G, Romanello V, Masiero E, Rudolf R, Del Piccolo P, Burden SJ, Di Lisi R, Sandri C & Zhao J et al. 2007 FoxO3 controls autophagy in skeletal muscle in vivo. Cell Metabolism 6 458471. (https://doi.org/10.1016/j.cmet.2007.11.001)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Marchal S, Cassar-Malek I, Pons F, Wrutniak C & Cabello G 1993 Triiodothyronine influences quail myoblast proliferation and differentiation. Biology of the Cell 78 191197. (https://doi.org/10.1016/0248-4900(93)90129-3)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Marsili A, Ramadan W, Harney JW, Mulcahey M, Castroneves LA, Goemann IM, Wajner SM, Huang SA, Zavacki AM & Maia AL et al. 2010 Type 2 iodothyronine deiodinase levels are higher in slow-twitch than fast-twitch mouse skeletal muscle and are increased in hypothyroidism. Endocrinology 151 59525960. (https://doi.org/10.1210/en.2010-0631)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Mebis L, Debaveye Y, Visser TJ & Van den Berghe G 2006 Changes within the thyroid axis during the course of critical illness. Endocrinology Metabolism Clinics of North America 35 807821, x. (https://doi.org/10.1016/j.ecl.2006.09.009)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Mebis L, Paletta D, Debaveye Y, Ellger B, Langouche L, D’Hoore A, Darras VM, Visser TJ & Van den Berghe G 2009 Expression of thyroid hormone transporters during critical illness. European Journal of Endocrinology 161 243250. (https://doi.org/10.1530/EJE-09-0290)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Milanesi A, Lee JW, Kim NH, Liu YY, Yang A, Sedrakyan S, Kahng A, Cervantes V, Tripuraneni N & Cheng SY et al. 2016 Thyroid hormone receptor α plays an essential role in male skeletal muscle myoblast proliferation, differentiation, and response to injury. Endocrinology 157 415. (https://doi.org/10.1210/en.2015-1443)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Mishra P, Varuzhanyan G, Pham AH & Chan DC 2015 Mitochondrial dynamics is a distinguishing feature of skeletal muscle fiber types and regulates organellar compartmentalization. Cell Metabolism 22 10331044. (https://doi.org/10.1016/j.cmet.2015.09.027)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Mitchell CS, Savage DB, Dufour S, Schoenmakers N, Murgatroyd P, Befroy D, Halsall D, Northcott S, Raymond-Barker P & Curran S et al. 2010 Resistance to thyroid hormone is associated with raised energy expenditure, muscle mitochondrial uncoupling, and hyperphagia. Journal of Clinical Investigation 120 13451354. (https://doi.org/10.1172/JCI38793)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Miyabara EH, Aoki MS, Soares AG, Saltao RM, Vilicev CM, Passarelli M, Scanlan TS, Gouveia CH & Moriscot AS 2005 Thyroid hormone receptor-beta-selective agonist GC-24 spares skeletal muscle type I to II fiber shift. Cell and Tissue Research 321 233241. (https://doi.org/10.1007/s00441-005-1119-3)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Muller A, van der Linden GC, Zuidwijk MJ, Simonides WS, van der Laarse WJ & van Hardeveld C 1994 Differential effects of thyroid hormone on the expression of sarcoplasmic reticulum Ca(2+)-ATPase isoforms in rat skeletal muscle fibers. Biochemical and Biophysical Research Communications 203 10351042. (https://doi.org/10.1006/bbrc.1994.2286)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ortiga-Carvalho TM, Sidhaye AR & Wondisford FE 2015 Thyroid hormone receptors and resistance to thyroid hormone disorders. Nature Reviews Endocrinology 10 582591. (https://doi.org/10.1038/nrendo.2014.143)

    • Search Google Scholar
    • Export Citation
  • Ortiga-Carvalho TM, Chiamolera MI, Pazos-Moura CC & Wondisford FE 2016 Hypothalamus-pituitary-thyroid axis. Comprehensive Physiology 6 13871428.

  • Oustanina S, Hause G & Braun T 2004 Pax7 directs postnatal renewal and propagation of myogenic satellite cells but not their specification. EMBO Journal 23 34303439. (https://doi.org/10.1038/sj.emboj.7600346)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Pallud S, Ramauge M, Gavaret JM, Lennon AM, Munsch N, St Germain DL, Pierre M & Courtin F 1999 Regulation of type 3 iodothyronine deiodinase expression in cultured rat astrocytes: role of the Erk cascade. Endocrinology 140 29172923. (https://doi.org/10.1210/endo.140.6.6834)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Pelletier P, Gauthier K, Sideleva O, Samarut J & Silva JE 2008 Mice lacking the thyroid hormone receptor-alpha gene spend more energy in thermogenesis, burn more fat, and are less sensitive to high-fat diet-induced obesity. Endocrinology 149 64716486. (https://doi.org/10.1210/en.2008-0718)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ramadan W, Marsili A, Huang S, Larsen PR & Silva JE 2011 Type-2 iodothyronine 5′deiodinase in skeletal muscle of C57BL/6 mice. I. Identity, subcellular localization, and characterization. Endocrinology 152 30823092. (https://doi.org/10.1210/en.2011-0137)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Relaix F, Montarras D, Zaffran S, Gayraud-Morel B, Rocancourt D, Tajbakhsh S, Mansouri A, Cumano A & Buckingham M 2006 Pax3 and Pax7 have distinct and overlapping functions in adult muscle progenitor cells. Journal of Cell Biology 172 91102. (https://doi.org/10.1083/jcb.200508044)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Rodriguez-Perez A, Palos-Paz F, Kaptein E, Visser TJ, Dominguez-Gerpe L, Alvarez-Escudero J & Lado-Abeal J 2008 Identification of molecular mechanisms related to nonthyroidal illness syndrome in skeletal muscle and adipose tissue from patients with septic shock. Clinical Endocrinology 68 821827. (https://doi.org/10.1111/j.1365-2265.2007.03102.x)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Salvatore D, Simonides WS, Dentice M, Zavacki AM & Larsen PR 2014 Thyroid hormones and skeletal muscle – new insights and potential implications. Nature Reviews Endocrinology 10 206214. (https://doi.org/10.1038/nrendo.2013.238)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Santalucía T, Moreno H, Palacín M, Yacoub MH, Brand NJ & Zorzano A 2001 A novel functional co-operation between MyoD, MEF2 and TRalpha1 is sufficient for the induction of GLUT4 gene transcription. Journal of Molecular Biology 314 195204.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Schiaffino S & Reggiani C 2011 Fiber types in mammalian skeletal muscles. Physiological Reviews 91 14471531. (https://doi.org/10.1152/physrev.00031.2010)

    • Search Google Scholar
    • Export Citation
  • Schiaffino S, Hanzlíková V & Pierobon S 1970 Relations between structure and function in rat skeletal muscle fibers. Journal of Cell Biology 47 107119. (https://doi.org/10.1083/jcb.47.1.107)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Schiaffino S, Gorza L, Pitton G, Saggin L, Ausoni S, Sartore S & Lømo T 1988 Embryonic and neonatal myosin heavy chain in denervated and paralyzed rat skeletal muscle. Developmental Biology 127 111. (https://doi.org/10.1016/0012-1606(88)90183-2)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Schiaffino S, Rossi AC, Smerdu V, Leinwand LA & Reggiani C 2015 Developmental myosins: expression patterns and functional significance. Skeletal Muscle 5 22. (https://doi.org/10.1186/s13395-015-0046-6)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Schneider MJ, Fiering SN, Pallud SE, Parlow AF, St Germain DL & Galton VA 2001 Targeted disruption of the type 2 selenodeiodinase gene (DIO2) results in a phenotype of pituitary resistance to T4. Molecular Endocrinology 15 21372148. (https://doi.org/10.1210/mend.15.12.0740)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Schnyder S & Handschin C 2015 Skeletal muscle as an endocrine organ: PGC-1α, myokines and exercise. Bone 80 115125. (https://doi.org/10.1016/j.bone.2015.02.008)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Schwartz CE & Stevenson RE 2007 The MCT8 thyroid hormone transporter and Allan-Herndon-Dudley syndrome. Best Practice and Research Clinical Endocrinology and Metabolism 21 307321. (https://doi.org/10.1016/j.beem.2007.03.009)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Simonides WS & van Hardeveld C 1989 The postnatal development of sarcoplasmic reticulum Ca2+ transport activity in skeletal muscle of the rat is critically dependent on thyroid hormone. Endocrinology 124 11451152. (https://doi.org/10.1210/endo-124-3-1145)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Simonides WS, Brent GA, Thelen MH, van der Linden CG, Larsen PR & van Hardeveld C 1996 Characterization of the promoter of the rat sarcoplasmic endoplasmic reticulum Ca2+-ATPase 1 gene and analysis of thyroid hormone responsiveness. Journal of Biological Chemistry 271 3204832056. (https://doi.org/10.1074/jbc.271.50.32048)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Simonides WS & van Hardeveld C 2008 Thyroid hormone as a determinant of metabolic and contractile phenotype of skeletal muscle. Thyroid 18 205216. (https://doi.org/10.1089/thy.2007.0256)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Slater CR 1982 Postnatal maturation of nerve-muscle junctions in hindlimb muscles of the mouse. Developmental Biology 94 1122. (https://doi.org/10.1016/0012-1606(82)90063-X)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Solmonson A & Mills EM 2016 Uncoupling proteins and the molecular mechanisms of thyroid thermogenesis. Endocrinology 157 455462. (https://doi.org/10.1210/en.2015-1803)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Stienen GJ, Kiers JL, Bottinelli R & Reggiani C 1996 Myofibrillar ATPase activity in skinned human skeletal muscle fibres: fibre type and temperature dependence. Journal of Physiology 493 299307. (https://doi.org/10.1113/jphysiol.1996.sp021384)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Torrance CJ, Usala SJ, Pessin JE & Dohm GL 1997 Characterization of a low affinity thyroid hormone receptor binding site within the rat GLUT4 gene promoter. Endocrinology 138 12151223. (https://doi.org/10.1210/endo.138.3.4982)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Van den Berghe G 2016 On the neuroendocrinopathy of critical illness: perspectives for feeding and novel treatments. American Journal of Respiratory and Critical Care Medicine 194 13371348.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • van der Linden GC, Simonides WS & van Hardeveld C 1992 Thyroid hormone regulates Ca(2+)-ATPase mRNA levels of sarcoplasmic reticulum during neonatal development of fast skeletal muscle. Molecular and Cellular Endocrinology 90 125131. (https://doi.org/10.1016/0303-7207(92)90110-R)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Vidal-Puig AJ, Grujic D, Zhang CY, Hagen T, Boss O, Ido Y, Szczepanik A, Wade J, Mootha V & Cortright R et al. 2000 Energy metabolism in uncoupling protein 3 gene knockout mice. Journal of Biological Chemistry 275 1625816266. (https://doi.org/10.1074/jbc.M910179199)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Visser WE, Heemstra KA, Swagemakers SM, Ozgür Z, Corssmit EP, Burggraaf J, van Ijcken WF, van der Spek PJ, Smit JW & Visser TJ 2009 Physiological thyroid hormone levels regulate numerous skeletal muscle transcripts. Journal of Clinical Endocrinology and Metabolism 94 34873496. (https://doi.org/10.1210/jc.2009-0782)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Wajner SM, Goemann IM, Bueno AL, Larsen PR & Maia AL 2011 IL-6 promotes nonthyroidal illness syndrome by blocking thyroxine activation while promoting thyroid hormone inactivation in human cells. Journal of Clinical Investigation 121 18341845.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Weinstein SP, O’Boyle E & Haber RS 1994 Thyroid hormone increases basal and insulin-stimulated glucose transport in skeletal muscle. The role of GLUT4 glucose transporter expression. Diabetes 43 11851189. (https://doi.org/10.2337/diab.43.10.1185)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Werneck-de-Castro JP, Fonseca T, Ignacio DL, Fernandes GW, Andrade C, Lartey L, Ribeiro MB, Ribeiro MO, Gereben B & Bianco AC 2015 Thyroid hormone signaling in male mouse skeletal muscle is largely independent of D2 in myocytes. Endocrinology 156 38423852. (https://doi.org/10.1210/en.2015-1246)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wulf A, Harneit A, Kröger M, Kebenko M, Wetzel MG & Weitzel JM 2008 T3-mediated expression of PGC-1alpha via a far upstream located thyroid hormone response element. Molecular and Cellular Endocrinology 287 9095. (https://doi.org/10.1016/j.mce.2008.01.017)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Yu F, Göthe S, Wikström L, Forrest D, Vennström B & Larsson L 2000 Effects of thyroid hormone receptor gene disruption on myosin isoform expression in mouse skeletal muscles. American Journal of Physiology: Regulatory and Integrative Computational Physiology 278 R1545R1554.

    • Search Google Scholar
    • Export Citation
  • Zeold A, Pormuller L, Dentice M, Harney JW, Curcio-Morelli C, Tente SM, Bianco AC & Gereben B 2006 Metabolic instability of type 2 deiodinase is transferable to stable proteins independently of subcellular localization. Journal of Biological Chemistry 281 3153831543. (https://doi.org/10.1074/jbc.M604728200)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Zhang D, Wang X, Li Y, Zhao L, Lu M, Yao X, Xia H, Wang YC, Liu MF & Jiang J et al. 2014 Thyroid hormone regulates muscle fiber type conversion via miR-133a1. Journal of Cell Biology 207 753766. (https://doi.org/10.1083/jcb.201406068)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Zolfaghari PS, Carre JE, Parker N, Curtin NA, Duchen MR & Singer M 2015 Skeletal muscle dysfunction is associated with derangements in mitochondrial bioenergetics (but not UCP3) in a rodent model of sepsis. American Journal of Physiology: Endocrinology and Metabolism 308 E713E725. (https://doi.org/10.1152/ajpendo.00562.2014)

    • Crossref
    • Search Google Scholar
    • Export Citation

 

Society for Endocrinology logo

  • View in gallery

    Characteristics of the different fibre types of muscle and TH regulation. (A) SM presents hybrid fibre types I, IIa, IIx and IIb, which have particular characteristics. Slow fibre type I presents MHY7, while the rapid fibre type IIa has MYH2, fibre type IIx has MYH1 and fibre type IIb has MYH4. Phosphocreatine content is greater in glycolytic IIa and IIb fibres, whereas type II and IIa fibres are more oxidative and have higher mitochondria content. The presence of myoglobin in the cytoplasm gives the reddish colouration, which is expressive in type I fibres and decreases gradually through IIa and IIx fibres and is absent in IIb fibres. Slow fibres present poorly developed SR in contrast to a well-developed SR in fast fibres. Type I fibres express SERCA2a, and type IIa, IIx and IIb fibres present SERCA1a/b. Slow and fast oxidative muscle fibres present higher expression of GLUT4, and at rest, fast fibres accumulate more glycogen than slow fibres. (B) TH induces the fibre type switch to a faster profile of the contraction–relaxation cycle. THs repress slow type I fibre MYH7 expression and stimulate the rapid type II fibres’ MYH-2, -1, and -4 expression. TH-induced expression of SERCA 1a and 2a increases relaxation. Local conversion of T4 to T3, via D2, promotes increased stability of Slc2a4 (GLUT4) mRNA through polyadenylation, which increases the stability and translocation to the sarcolemma. TH increases oxidative capacity due to an increase in mitochondrial content and its protein activity. These regulations occur by nuclear and mitochondrial genome pathways, mediated by THR and p43, respectively, and also by increased Pgc1a expression. TH stimulates UCP3 expression that uncouples ATP synthesis. Overall, TH increases oxygen consumption and the resting metabolic rate.

  • View in gallery

    Myogenesis and TH. The SC niches are next to blood vessels, between the basal lamina and the myofiber. Pax7 and Foxo3 are expressed by quiescent SCs, and these factors are involved in cell survival and self-renewal. Under the appropriate stimulus, SCs enter the differentiation pathway and thus turn into committed SCs expressing PAX7 and D3. The low intracellular T3 favors the survival and cell proliferation. The activated SCs express PAX7 and MYF5 and decrease the expression of D3; thus, intracellular T3 can increase and induce the expression of FOXO3, which induces the expression of D2 and represses D3. Both T3 and FOXO3 induce MYOD1 leading to the progression of the differentiation of activated SC into the proliferative myoblast. In these, THRA1 represses MYOD1 and myogenin expression, whereas MYOD1 induces Thra1 expression. Additionally, FOXO3 induces D2 expression, leading to an increase in intracellular T3, which represses AP1 and induces the expression of MYOD1 and myogenin. T3, MYF4 and myogenin are involved in the terminal differentiation of myocytes into myotubes/myofibers, and these factors stimulate the expression of MYH and SERCA.

  • Adams GR, Haddad F & Baldwin KM 2000 The interaction of space flight and thyroid state on somatic and skeletal muscle growth and myosin heavy chain expression on neonatal rodents. Journal of Gravitational Physiology 7 P15P18.

    • Search Google Scholar
    • Export Citation
  • Ambrosio R, De Stefano MA, Di Girolamo D & Salvatore D 2017 Thyroid hormone signaling and deiodinase actions in muscle stem/progenitor cells. Molecular and Cellular Endocrinology [epub]. (https://doi.org/10.1016/j.mce.2017.06.014)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Amorim BS, Ueta CB, Freitas BC, Nassif RJ, Gouveia CH, Christoffolete MA, Moriscot AS, Lancelloti CL, Llimona F & Barbeiro HV et al. 2009 A TRbeta-selective agonist confers resistance to diet-induced obesity. Journal of Endocrinology 203 291299. (https://doi.org/10.1677/JOE-08-0539)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Anderson JE, McIntosh LM, Moor AN & Yablonka-Reuveni Z 1998 Levels of MyoD protein expression following injury of mdx and normal limb muscle are modified by thyroid hormone. Journal of Histochemistry and Cytochemistry 46 5967. (https://doi.org/10.1177/002215549804600108)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Argilés JM, Campos N, Lopez-Pedrosa JM, Rueda R & Rodriguez-Mañas L 2016 Skeletal muscle regulates metabolism via interorgan crosstalk: roles in health and disease. Journal of the American Medical Directors Association 17 789796. (https://doi.org/10.1016/j.jamda.2016.04.019)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bahi L, Garnier A, Fortin D, Serrurier B, Veksler V, Bigard AX & Ventura-Clapier R 2005 Differential effects of thyroid hormones on energy metabolism of rat slow- and fast-twitch muscles. Journal of Cellular Physiology 203 589598. (https://doi.org/10.1002/jcp.20273)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Baldwin KM & Haddad F 2001 Effects of different activity and inactivity paradigms on myosin heavy chain gene expression in striated muscle. Journal of Applied Physiology 90 345357.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Bannett RR, Sampson SR & Shainberg A 1984 Influence of thyroid hormone on some electrophysiological properties of developing rat skeletal muscle cells in culture. Brain Research 294 7582. (https://doi.org/10.1016/0006-8993(84)91311-8)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Barbe P, Larrouy D, Boulanger C, Chevillotte E, Viguerie N, Thalamas C, Oliva Trastoy M, Roques M, Vidal H & Langin D 2001 Triiodothyronine-mediated up-regulation of UCP2 and UCP3 mRNA expression in human skeletal muscle without coordinated induction of mitochondrial respiratory chain genes. FASEB Journal 15 1315. (https://doi.org/10.1096/fj.00-0502fje)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Bárez-López S, Bosch-García D, Gómez-Andrés D, Pulido-Valdeolivas I, Montero-Pedrazuela A, Obregon MJ & Guadaño-Ferraz A 2014 Abnormal motor phenotype at adult stages in mice lacking type 2 deiodinase. PLoS ONE 9 e103857. (https://doi.org/10.1371/journal.pone.0103857)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Beermann DH, Hood LF & Liboff M 1983 Satellite cell and myonuclei populations in rat soleus and extensor digitorum longus muscles after maternal nutritional deprivation and realimentation. Journal of Animal Science 57 16181625. (https://doi.org/10.2527/jas1983.5761618x)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bentzinger CF, Wang YX & Rudnicki MA 2012 Building muscle: molecular regulation of myogenesis. Cold Spring Harbor Perspectives in Biology 4 a008342. (https://doi.org/10.1101/cshperspect.a008342)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bianco AC, Salvatore D, Gereben B, Berry MJ & Larsen PR 2002 Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases. Endocrine Reviews 23 3889. (https://doi.org/10.1210/edrv.23.1.0455)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bloise FF, van der Spek AH, Surovtseva OV, Ortiga-Carvalho TM, Fliers E & Boelen A 2016 Differential effects of sepsis and chronic inflammation on diaphragm muscle fiber type, thyroid hormone metabolism, and mitochondrial function. Thyroid 26 600609. (https://doi.org/10.1089/thy.2015.0536)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bocco BM, Louzada RA, Silvestre DH, Santos MC, Anne-Palmer E, Rangel IF, Abdalla S, Ferreira AC, Ribeiro MO & Gereben B et al. 2016 Thyroid hormone activation by type 2 deiodinase mediates exercise-induced peroxisome proliferator-activated receptor-γ coactivator-1α expression in skeletal muscle. Journal of Physiology 594 52555269. (https://doi.org/10.1113/JP272440)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Boelen A, Kwakkel J & Fliers E 2011 Beyond low plasma T3: local thyroid hormone metabolism during inflammation and infection. Endocrine Reviews 32 670693. (https://doi.org/10.1210/er.2011-0007)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Boelen A, van der Spek AH, Bloise F, de Vries EM, Surovtseva OV, van Beeren M, Ackermans MT, Kwakkel J & Fliers E 2017 Tissue thyroid hormone metabolism is differentially regulated during illness in mice. Journal of Endocrinology 233 2536. (https://doi.org/10.1530/JOE-16-0483)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Brockmann K, Dumitrescu AM, Best TT, Hanefeld F & Refetoff S 2005 X-linked paroxysmal dyskinesia and severe global retardation caused by defective MCT8 gene. Journal of Neurology 252 663666. (https://doi.org/10.1007/s00415-005-0713-3)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Brunetto EL, Teixeira SAS, Giannocco G, Machado UF & Nunes MT 2012 T3 rapidly increases SLC2A4 gene expression and GLUT4 trafficking to the plasma membrane in skeletal muscle of rat and improves glucose homeostasis. Thyroid 22 7079. (https://doi.org/10.1089/thy.2010.0409)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Busson M, Daury L, Seyer P, Grandemange S, Pessemesse L, Casas F, Wrutniak-Cabello C & Cabello G 2006 Avian MyoD and c-Jun coordinately induce transcriptional activity of the 3,5,3′-triiodothyronine nuclear receptor c-ErbAalpha1 in proliferating myoblasts. Endocrinology 147 34083418. (https://doi.org/10.1210/en.2006-0101)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Butler-Browne GS, Herlicoviez D & Whalen RG 1984 Effects of hypothyroidism on myosin isozyme transitions in developing rat muscle. FEBS Letters 166 7175. (https://doi.org/10.1016/0014-5793(84)80047-2)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Carnac G, Albagli-Curiel O, Vandromme M, Pinset C, Montarras D, Laudet V & Bonnieu A 1992 3,5,3′-Triiodothyronine positively regulates both MyoD1 gene transcription and terminal differentiation in C2 myoblasts. Molecular Endocrinology 6 11851194. (https://doi.org/10.1210/mend.6.8.1406697)

    • Search Google Scholar
    • Export Citation
  • Cassar-Malek I, Marchal S, Rochard P, Casas F, Wrutniak C, Samarut J & Cabello G 1996 Induction of c-Erb A-AP-1 interactions and c-Erb A transcriptional activity in myoblasts by RXR. Consequences for muscle differentiation. Journal of Biological Chemistry 271 1139211399. (https://doi.org/10.1074/jbc.271.19.11392)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Christov C, Chrétien F, Abou-Khalil R, Bassez G, Vallet G, Authier FJ, Bassaglia Y, Shinin V, Tajbakhsh S & Chazaud B et al. 2007 Muscle satellite cells and endothelial cells: close neighbors and privileged partners. Molecular Biology of the Cell 18 13971409. (https://doi.org/10.1091/mbc.E06-08-0693)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Clapham JC, Arch JR, Chapman H, Haynes A, Lister C, Moore GB, Piercy V, Carter SA, Lehner I & Smith SA et al. 2000 Mice overexpressing human uncoupling protein-3 in skeletal muscle are hyperphagic and lean. Nature 406 415418. (https://doi.org/10.1038/35019082)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Collins CA, Gnocchi VF, White RB, Boldrin L, Perez-Ruiz A, Relaix F, Morgan JE & Zammit PS 2009 Integrated functions of Pax3 and Pax7 in the regulation of proliferation, cell size and myogenic differentiation. PLoS ONE 4 e4475. (https://doi.org/10.1371/journal.pone.0004475)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Cordeiro A, Souza LL, Einicker-Lamas M & Pazos-Moura CC 2013 Non-classic thyroid hormone signalling involved in hepatic lipid metabolism. Journal of Endocrinology 216 R47R57. (https://doi.org/10.1530/JOE-12-0542)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Cormery B, Beaumont E, Csukly K & Gardiner P 2005 Hindlimb unweighting for 2 weeks alters physiological properties of rat hindlimb motoneurones. Journal of Physiology 568 841850. (https://doi.org/10.1113/jphysiol.2005.091835)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • D’Arezzo S, Incerpi S, Davis FB, Acconcia F, Marino M, Farias RN & Davis PJ 2004 Rapid nongenomic effects of 3,5,3′-triiodo-L-thyronine on the intracellular pH of L-6 myoblasts are mediated by intracellular calcium mobilization and kinase pathways. Endocrinology 145 56945703. (https://doi.org/10.1210/en.2004-0890)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Daury L, Busson M, Casas F, Cassar-Malek I, Wrutniak-Cabello C & Cabello G 2001 The triiodothyronine nuclear receptor c-ErbAalpha1 inhibits avian MyoD transcriptional activity in myoblasts. FEBS Letters 508 236240. (https://doi.org/10.1016/S0014-5793(01)03063-0)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • de Lange P, Lanni A, Beneduce L, Moreno M, Lombardi A, Silvestri E & Goglia F 2001 Uncoupling protein-3 is a molecular determinant for the regulation of resting metabolic rate by thyroid hormone. Endocrinology 142 34143420. (https://doi.org/10.1210/endo.142.8.8303)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Dentice M, Marsili A, Ambrosio R, Guardiola O, Sibilio A, Paik JH, Minchiotti G, DePinho RA, Fenzi G & Larsen PR et al. 2010 The FoxO3/type 2 deiodinase pathway is required for normal mouse myogenesis and muscle regeneration. Journal of Clinical Investigation 120 40214030. (https://doi.org/10.1172/JCI43670)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Dentice M, Ambrosio R, Damiano V, Sibilio A, Luongo C, Guardiola O, Yennek S, Zordan P, Minchiotti G & Colao A et al. 2014 Intracellular inactivation of thyroid hormone is a survival mechanism for muscle stem cell proliferation and lineage progression. Cell Metabolism 20 10381048. (https://doi.org/10.1016/j.cmet.2014.10.009)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Di Cosmo C, Liao XH, Ye H, Ferrara AM, Weiss RE, Refetoff S & Dumitrescu AM 2013 Mct8-deficient mice have increased energy expenditure and reduced fat mass that is abrogated by normalization of serum T3 levels. Endocrinology 154 48854895. (https://doi.org/10.1210/en.2013-1150)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • di Maso NA, Caiozzo VJ & Baldwin KM 2000 Single-fiber myosin heavy chain polymorphism during postnatal development: modulation by hypothyroidism. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology 278 R1099R1106.

    • Search Google Scholar
    • Export Citation
  • Downes M, Griggs R, Atkins A, Olson EN & Muscat GE 1993 Identification of a thyroid hormone response element in the mouse myogenin gene: characterization of the thyroid hormone and retinoid X receptor heterodimeric binding site. Cell Growth and Differentiation 4 901909.

    • Search Google Scholar
    • Export Citation
  • Dumont NA, Bentzinger CF, Sincennes MC & Rudnicki MA 2015a Satellite cells and skeletal muscle regeneration. Comprehensive Physiology 5 10271059. (https://doi.org/10.1002/cphy.c140068)

    • Search Google Scholar
    • Export Citation
  • Dümmler K, Müller S & Seitz HJ 1996 Regulation of adenine nucleotide translocase and glycerol 3-phosphate dehydrogenase expression by thyroid hormones in different rat tissues. Biochemical Journal 317 913918.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Dumont NA, Wang YX & Rudnicki MA 2015b Intrinsic and extrinsic mechanisms regulating satellite cell function. Development 142 15721581. (https://doi.org/10.1242/dev.114223)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Fliers E, Kalsbeek A & Boelen A 2014 Beyond the fixed setpoint of the hypothalamus-pituitary-thyroid axis. European Journal of Endocrinology 171 R197R208. (https://doi.org/10.1530/EJE-14-0285)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Fliers E, Bianco AC, Langouche L & Boelen A 2015 Thyroid function in critically ill patients. Lancet Diabetes and Endocrinology 3 816825. (https://doi.org/10.1016/S2213-8587(15)00225-9)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Fredriksson K & Rooyackers O 2007 Mitochondrial function in sepsis: respiratory versus leg muscle. Critical Care Medicine 35 S449S453. (https://doi.org/10.1097/01.CCM.0000278048.00896.4B)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Fredriksson K, Radell P, Eriksson LI, Hultenby K & Rooyackers O 2005 Effect of prolonged mechanical ventilation on diaphragm muscle mitochondria in piglets. Acta Anaesthesiologica Scandinavica 49 11011107. (https://doi.org/10.1111/j.1399-6576.2005.00718.x)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Fredriksson K, Hammarqvist F, Strigard K, Hultenby K, Ljungqvist O, Wernerman J & Rooyackers O 2006 Derangements in mitochondrial metabolism in intercostal and leg muscle of critically ill patients with sepsis-induced multiple organ failure. American Journal of Physiology: Endocrinology and Metabolism 291 E1044E1050. (https://doi.org/10.1152/ajpendo.00218.2006)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Gambke B, Lyons GE, Haselgrove J, Kelly AM & Rubinstein NA 1983 Thyroidal and neural control of myosin transitions during development of rat fast and slow muscles. FEBS Letters 156 335339. (https://doi.org/10.1016/0014-5793(83)80524-9)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Gereben B & Salvatore D 2005 Pretranslational regulation of type 2 deiodinase. Thyroid 15 855864. (https://doi.org/10.1089/thy.2005.15.855)

  • Gong DW, He Y, Karas M & Reitman M 1997 Uncoupling protein-3 is a mediator of thermogenesis regulated by thyroid hormone, beta3-adrenergic agonists, and leptin. Journal of Biological Chemistry 272 2412924132. (https://doi.org/10.1074/jbc.272.39.24129)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Gong DW, Monemdjou S, Gavrilova O, Leon LR, Marcus-Samuels B, Chou CJ, Everett C, Kozak LP, Li C &