Testosterone improves muscle fiber asset and exercise performance in a metabolic syndrome model

in Journal of Endocrinology
Authors:
Erica Sarchielli Anatomy and Histology Unit, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy

Search for other papers by Erica Sarchielli in
Current site
Google Scholar
PubMed Close
,
Paolo Comeglio Sexual Medicine and Andrology Unit, Department of Biomedical, Experimental and Clinical Sciences ‘Mario Serio’, University of Florence, Florence, Italy

Search for other papers by Paolo Comeglio in
Current site
Google Scholar
PubMed Close
,
Sandra Filippi Interdepartmental Laboratory of Functional and Cellular Pharmacology of Reproduction, Department of Neuroscience, Drug Research and Child Care, University of Florence, Florence, Italy

Search for other papers by Sandra Filippi in
Current site
Google Scholar
PubMed Close
,
Ilaria Cellai Sexual Medicine and Andrology Unit, Department of Biomedical, Experimental and Clinical Sciences ‘Mario Serio’, University of Florence, Florence, Italy

Search for other papers by Ilaria Cellai in
Current site
Google Scholar
PubMed Close
,
Giulia Guarnieri Anatomy and Histology Unit, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy

Search for other papers by Giulia Guarnieri in
Current site
Google Scholar
PubMed Close
,
Daniele Guasti Anatomy and Histology Unit, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy

Search for other papers by Daniele Guasti in
Current site
Google Scholar
PubMed Close
,
Elena Rapizzi Sexual Medicine and Andrology Unit, Department of Biomedical, Experimental and Clinical Sciences ‘Mario Serio’, University of Florence, Florence, Italy

Search for other papers by Elena Rapizzi in
Current site
Google Scholar
PubMed Close
,
Giulia Rastrelli Sexual Medicine and Andrology Unit, Department of Biomedical, Experimental and Clinical Sciences ‘Mario Serio’, University of Florence, Florence, Italy

Search for other papers by Giulia Rastrelli in
Current site
Google Scholar
PubMed Close
,
Daniele Bani Anatomy and Histology Unit, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy

Search for other papers by Daniele Bani in
Current site
Google Scholar
PubMed Close
,
Gabriella Vannelli Anatomy and Histology Unit, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy

Search for other papers by Gabriella Vannelli in
Current site
Google Scholar
PubMed Close
,
Linda Vignozzi Sexual Medicine and Andrology Unit, Department of Biomedical, Experimental and Clinical Sciences ‘Mario Serio’, University of Florence, Florence, Italy
I.N.B.B. (Istituto Nazionale Biostrutture e Biosistemi), Rome, Italy
Andrology, Women’s Endocrinology and Gender Incongruence, Careggi Hospital, Florence, Italy

Search for other papers by Linda Vignozzi in
Current site
Google Scholar
PubMed Close
,
Annamaria Morelli Anatomy and Histology Unit, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy

Search for other papers by Annamaria Morelli in
Current site
Google Scholar
PubMed Close
, and
Mario Maggi Sexual Medicine and Andrology Unit, Department of Biomedical, Experimental and Clinical Sciences ‘Mario Serio’, University of Florence, Florence, Italy
I.N.B.B. (Istituto Nazionale Biostrutture e Biosistemi), Rome, Italy
Endocrinology, Careggi Hospital, Florence, Italy

Search for other papers by Mario Maggi in
Current site
Google Scholar
PubMed Close

Correspondence should be addressed to A Morelli: a.morelli@unifi.it
DOI:
https://doi.org/10.1530/JOE-19-0532
Volume/Issue:
Volume 245: Issue 2
Article Type:
Research Article
Page Range:
259–279
Online Publication Date:
May 2020
Copyright:
© 2020 Society for Endocrinology 2020
Restricted access
Rent on DeepDyve

Sign up for journal news

Lifestyle modifications, including physical exercise (PhyEx), are well-known treatments for metabolic syndrome (MetS), a cluster of metabolic and cardiovascular risk factors often associated to hypogonadism. Given the trophic role of testosterone on skeletal muscle (SkM), this study was aimed at evaluating the effects of testosterone treatment on SkM metabolism and exercise performance in male rabbits with high-fat diet (HFD)-induced MetS. HFD rabbits, treated or not with testosterone (30 mg/kg/week) for 12 weeks, were compared to regular diet animals (RD). A subset of each group was exercise-trained for 12 weeks. HFD increased type-II (fast, glycolytic) and decreased type-I (slow, oxidative) muscle fibers compared to RD as evaluated by RT-PCR and histochemistry. Testosterone reverted these effects, also inducing the expression of mitochondrial respiration enzymes and normalizing HFD-induced mitochondrial cristae reduction. Moreover, testosterone significantly increased the expression of myogenic/differentiation markers and genes related to glucidic/lipid metabolism. At the end of the PhyEx protocol, when compared to RD, HFD rabbits showed a significant reduction of running distance and running time, while testosterone counteracted this effect, also decreasing lactate production. In the trained groups, muscle histology showed a significant reduction of oxidative fibers in HFD compared to RD and the positive effect of testosterone in maintaining oxidative metabolism, as also demonstrated by analyzing mitochondrial ultrastructure, succinate dehydrogenase activity and ATP production. Our results indicate that testosterone could be useful to promote oxidative muscle metabolism altered by MetS, thus improving exercise performance. Conversely, testosterone administration to otherwise eugonadal rabbits (RD) only increased muscle fiber diameter but not endurance performance.

Journal of Endocrinology is committed to supporting researchers in demonstrating the impact of their articles published in the journal.

The two types of article metrics we measure are (i) more traditional full-text views and pdf downloads, and (ii) Altmetric data, which shows the wider impact of articles in a range of non-traditional sources, such as social media.

More information is on the Reasons to publish page.

Sept 2018 onwards Past Year Past 30 Days
Full Text Views 2161 63 3
PDF Downloads 1429 58 7

 

  • Collapse
  • Expand
Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© 2020 Society for Endocrinology 2020
Page(s):
21
Article Type:
Research Article
Received Date:
19 Feb 2020
Accepted Date:
05 Mar 2020
Print Publication Date:
01 May 2020
Online Publication Date:
May 2020
Keywords:
testosterone treatment; muscle metabolism; muscle fibers; physical activity; metabolic syndrome

  • Abrigo J, Rivera JC, Aravena J, Cabrera D, Simon F, Ezquer F, Ezquer M & Cabello-Verrugio C 2016 High fat diet-induced skeletal muscle wasting is decreased by Mesenchymal Stem Cells Administration: implications on oxidative stress, ubiquitin proteasome pathway activation, and myonuclear apoptosis. Oxidative Medicine and Cellular Longevity 2016 9047821. (https://doi.org/10.1155/2016/9047821)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Basaria S, Coviello AD, Travison TG, Storer TW, Farwell WR, Jette AM, Eder R, Tennstedt S, Ulloor J, Zhang A, et al. 2010 Adverse events associated with testosterone administration. New England Journal of Medicine 363 109–122. (https://doi.org/10.1056/NEJMoa1000485)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Baumgartner RN, Waters DL, Gallagher D, Morley JE & Garry PJ 1999 Predictors of skeletal muscle mass in elderly men and women. Mechanisms of Ageing and Development 107 123–136. (https://doi.org/10.1016/s0047-6374(98)00130-4)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Bhasin S, Storer TW, Berman N, Yarasheski KE, Clevenger B, Phillips J, Lee WP, Bunnell TJ & Casaburi R 1997 Testosterone replacement increases fat-free mass and muscle size in hypogonadal men. Journal of Clinical Endocrinology and Metabolism 82 407–413. (https://doi.org/10.1210/jcem.82.2.3733)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Bhasin S, Storer TW, Singh AB, Woodhouse L, Singh R, Artaza J, Taylor WE, Sinha-Hikim I, Jasuja R & Gonzalez-Cadavid N 2004 Testosterone effects on the skeletal muscle. In Testosterone: Action, Deficiency, Substitution, 3rd ed., pp. 255–282. Cambridge University Press.

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Bhasin S, Brito JP, Cunningham GR, Hayes FJ, Hodis HN, Matsumoto AM, Snyder PJ, Swerdloff RS, Wu FC & Yialamas MA 2018 Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. Journal of Clinical Endocrinology and Metabolism 103 1715–1744. (https://doi.org/10.1210/jc.2018-00229)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Bhatt BA, Dube JJ, Dedousis N, Reider JA & O’Doherty RM 2006 Diet-induced obesity and acute hyperlipidemia reduce IκBα levels in rat skeletal muscle in a fiber-type dependent manner. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology 290 R233–R240. (https://doi.org/10.1152/ajpregu.00097.2005)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Bird SR & Hawley JA 2017 Update on the effects of physical activity on insulin sensitivity in humans. BMJ Open Sport and Exercise Medicine 21 e000143. (https://doi.org/10.1136/bmjsem-2016-000143)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Bouillaud F, Alves-Guerra MC & Ricquier D 2016 UCPs, at the interface between bioenergetics and metabolism. Biochimica et Biophysica Acta 1863 2443–2456. (https://doi.org/10.1016/j.bbamcr.2016.04.013)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Brooks GA, Fahey TD & Baldwin KM 2005 Exercise Physiology: Human Bioenergetics and Its Applications. New York: McGraw-Hill.

  • Cangiano B, Duminuco P, Vezzoli V, Guizzardi F, Chiodini I, Corona G, Maggi M, Persani L & Bonomi M 2019 Evidence for a common genetic origin of classic and milder adult-onset forms of isolated hypogonadotropic hypogonadism. Journal of Clinical Medicine 8 E126. (https://doi.org/10.3390/jcm8010126)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Carson JA & Manolagas SC 2015 Effects of sex steroids on bones and muscles: similarities, parallels, and putative interactions in health and disease. Bone 80 67–78. (https://doi.org/10.1016/j.bone.2015.04.015)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Chambon C, Duteil D, Vignaud A, Ferry A, Messaddeq N, Malivindi R, Kato S, Chambon P & Metzger D 2010 Myocytic androgen receptor controls the strength but not the mass of limb muscles. PNAS 107 14327–14332. (https://doi.org/10.1073/pnas.1009536107)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Church T 2011 Exercise in obesity, metabolic syndrome, and diabetes. Progress in Cardiovascular Diseases 53 412–418. (https://doi.org/10.1016/j.pcad.2011.03.013)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Coen PM, Musci RV, Hinkley JM & Miller BF 2018 Mitochondria as a target for mitigating sarcopenia. Frontiers in Physiology 9 1883. (https://doi.org/10.3389/fphys.2018.01883)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Corona G, Vignozzi L, Sforza A, Mannucci E & Maggi M 2015 Obesity and late-onset hypogonadism. Molecular and Cellular Endocrinology 418 120–133. (https://doi.org/10.1016/j.mce.2015.06.031)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Corona G, Giagulli VA, Maseroli E, Vignozzi L, Aversa A, Zitzmann M, Saad F, Mannucci E & Maggi M 2016 THERAPY OF ENDOCRINE DISEASE: Testosterone supplementation and body composition: results from a meta-analysis study. European Journal of Endocrinology 174 R99–R116. (https://doi.org/10.1530/EJE-15-0262)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Couplan E, Gelly C, Goubern M, Fleury C, Quesson B, Silberberg M, Thiaudiere E, Mateo P, Lonchampt M, Levens N, et al. 2002 High level of uncoupling protein 1 expression in muscle of transgenic mice selectively affects muscles at rest and decreases their IIb fiber content. Journal of Biological Chemistry 277 43079–43088. (https://doi.org/10.1074/jbc.M206726200)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Davey RA, Clarke MV, Russell PK, Rana K, Seto J, Roeszler KN, How JMY, Chia LY, North K & Zajac JD 2017 Androgen action via the androgen receptor in neurons within the brain positively regulates muscle mass in male mice. Endocrinology 158 3684–3695. (https://doi.org/10.1210/en.2017-00470)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • De Spiegeleer A, Beckwée D, Bautmans I, Petrovic M & Sarcopenia Guidelines Development group of the Belgian Society of Gerontology and Geriatrics (BSGG) 2018 Pharmacological interventions to improve muscle mass, muscle strength and physical performance in older people: an umbrella review of systematic reviews and meta-analyses. Drugs and Aging 35 719–734. (https://doi.org/10.1007/s40266-018-0566-y)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Denies MS, Johnson J, Maliphol AB, Bruno M, Kim A, Rizvi A, Rustici K & Medler S 2014 Diet-induced obesity alters skeletal muscle fiber types of male but not female mice. Physiological Reports 2 e00204. (https://doi.org/10.1002/phy2.204)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Filippi S, Vignozzi L, Morelli A, Chavalmane AK, Sarchielli E, Fibbi B, Saad F, Sandner P, Ruggiano P, Vannelli GB, et al. 2009 Testosterone partially ameliorates metabolic profile and erectile responsiveness to PDE5 inhibitors in an animal model of male metabolic syndrome. Journal of Sexual Medicine 6 3274–3288. (https://doi.org/10.1111/j.1743-6109.2009.01467.x)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Finkelstein JS, Lee H, Burnett-Bowie SA, Pallais JC, Yu EW, Borges LF, Jones BF, Barry CV, Wulczyn KE, Thomas BJ, et al. 2013 Gonadal steroids and body composition, strength, and sexual function in men. New England Journal of Medicine 369 1011–1022. (https://doi.org/10.1056/NEJMoa1206168)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Gonzalez BD, Jim HSL, Small BJ, Sutton SK, Fishman MN, Zachariah B, Heysek RV & Jacobsen PB 2016 Changes in physical functioning and muscle strength in men receiving androgen deprivation therapy for prostate cancer: a controlled comparison. Supportive Care in Cancer 24 2201–2207. (https://doi.org/10.1007/s00520-015-3016-y)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Gonzalez-Armenta JL, Gao Z, Appt SE, Vitolins MZ, Michalson KT, Register TC, Shively CA & Molina AJA 2019 Skeletal muscle mitochondrial respiration is elevated in female cynomolgus macaques fed a western compared with a Mediterranean diet. Journal of Nutrition 149 1493–1502. (https://doi.org/10.1093/jn/nxz092)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Grinspoon S, Corcoran C, Lee K, Burrows B, Hubbard J, Katznelson L, Walsh M, Guccione A, Cannan J, Heller H, et al. 1996 Loss of lean body and muscle mass correlates with androgen levels in hypogonadal men with acquired immunodeficiency syndrome and wasting. Journal of Clinical Endocrinology and Metabolism 81 4051–4058. (https://doi.org/10.1210/jcem.81.11.8923860)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Guo W, Wong S, Li M, Liang W, Liesa M, Serra C, Jasuja R, Bartke A, Kirkland JL, Shirihai O, et al. 2012 Testosterone plus low-intensity physical training in late life improves functional performance, skeletal muscle mitochondrial biogenesis, and mitochondrial quality control in male mice. PLoS ONE 7 e51180. (https://doi.org/10.1371/journal.pone.0051180)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Herbst KL & Bhasin S 2004 Testosterone action on skeletal muscle. Current Opinion in Clinical Nutrition and Metabolic Care 7 271–277. (https://doi.org/10.1097/00075197-200405000-00006)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Hernandez N, Torres SH, Vera O, De Sanctis JB & Flores E 2001 Muscle fiber composition and capillarization in relation to metabolic alterations in hypertensive men. Journal of Medicine 32 67–82.

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ingle L, Mellis M, Brodie D & Sandercock GR 2017 Associations between cardiorespiratory fitness and the metabolic syndrome in British men. Heart 103 524–528. (https://doi.org/10.1136/heartjnl-2016-310142)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Katterle Y, Keipert S, Hof J & Klaus S 2008 Dissociation of obesity and insulin resistance in transgenic mice with skeletal muscle expression of uncoupling protein 1. Physiological Genomics 32 352–359. (https://doi.org/10.1152/physiolgenomics.00194.2007)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Kovacheva EL, Hikim AP, Shen R, Sinha I & Sinha-Hikim I 2010 Testosterone supplementation reverses sarcopenia in aging through regulation of myostatin, c-Jun NH2-terminal kinase, Notch, and Akt signaling pathways. Endocrinology 151 628–638. (https://doi.org/10.1210/en.2009-1177)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Lakka TA & Laaksonen DE 2007 Physical activity in prevention and treatment of the metabolic syndrome. Applied Physiology, Nutrition, and Metabolism 32 76–88. (https://doi.org/10.1139/h06-113)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Lee SR, Khamoui AV, Jo E, Park BS, Zourdos MC, Panton LB, Ormsbee MJ & Kim JS 2015 Effects of chronic high fat feeding on skeletal muscle mass and function in middle-aged mice. Aging Clinical and Experimental Research 27 403–411. (https://doi.org/10.1007/s40520-015-0316-5)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Li B, Nolte LA, Ju JS, Han DH, Coleman T, Holloszy JO & Semenkovich CF 2000 Skeletal muscle respiratory uncoupling prevents diet-induced obesity and insulin resistance in mice. Nature Medicine 6 1115–1120. (https://doi.org/10.1038/80450)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Li S, Zhou X, Jo E, Mahzari A, Fouda S, Li D, Zhang K & Ye JM 2018 Preconditioning lessens high fat induced metabolic syndrome along with markers of increased metabolic capacity in muscle and adipose tissue. Bioscience Reports 38 BSR20181873. (https://doi.org/10.1042/BSR20181873)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • MacLean HE, Chiu WS, Notini AJ, Axell AM, Davey RA, McManus JF, Ma C, Plant DR, Lynch GS & Zajac JD 2008 Impaired skeletal muscle development and function in male, but not female, genomic androgen receptor knockout mice. FASEB Journal 22 2676–2689. (https://doi.org/10.1096/fj.08-105726)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Maneschi E, Morelli A, Filippi S, Cellai I, Comeglio P, Mazzanti B, Mello T, Calcagno A, Sarchielli E, Vignozzi L, et al. 2012 Testosterone treatment improves metabolic syndrome-induced adipose tissue derangements. Journal of Endocrinology 215 347–362. (https://doi.org/10.1530/JOE-12-0333)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • McCurdy CE, Schenk S, Hetrick B, Houck J, Drew BG, Kaye S, Lashbrook M, Bergman BC, Takahashi DL, Dean TA, et al. 2016 Maternal obesity reduces oxidative capacity in fetal skeletal muscle of Japanese macaques. JCI Insight 1 e86612. (https://doi.org/10.1172/jci.insight.86612)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Morelli A, Vignozzi L & Maggi M 2016 Hypogonadotropic hypogonadism and metabolic syndrome: insights from the high-fat diet experimental rabbit animal model. Minerva Endocrinologica 41 240–249.

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Morelli A, Filippi S, Comeglio P, Sarchielli E, Cellai I, Pallecchi M, Bartolucci G, Danza G, Rastrelli G, Corno C, et al. 2019 Physical activity counteracts metabolic syndrome-induced hypogonadotropic hypogonadism and erectile dysfunction in the rabbit. American Journal of Physiology: Endocrinology and Metabolism 316 E519–E535. (https://doi.org/10.1152/ajpendo.00377.2018)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Morley JE, Kaiser FE, Perry HM, Patrick P, Morley PM, Stauber PM, Vellas B, Baumgartner RN & Garry PJ 1997 Longitudinal changes in testosterone, luteinizing hormone, and follicle stimulating hormone in healthy older men. Metabolism: Clinical and Experimental 46 410–413. (https://doi.org/10.1016/s0026-0495(97)90057-3)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ophoff J, Van Proeyen K, Callewaert F, De Gendt K, De Bock K, Vanden Bosch A, Verhoeven G, Hespel P & Vanderschueren D 2009 Androgen signaling in myocytes contributes to the maintenance of muscle mass and fiber type regulation but not to muscle strength or fatigue. Endocrinology 150 3558–3566. (https://doi.org/10.1210/en.2008-1509)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Pedersen BK & Saltin B 2015 Exercise as medicine – evidence for prescribing exercise as therapy in 26 different chronic diseases. Scandinavian Journal of Medicine and Science in Sports 25 (Supplement 3) 1–72. (https://doi.org/10.1111/sms.12581)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Pette D 2002 The adaptive potential of skeletal muscle fibers. Canadian Journal of Applied Physiology 27 423–448. (https://doi.org/10.1139/h02-023)

  • Pitteloud N, Mootha VK, Dwyer AA, Hardin M, Lee H, Eriksson KF, Tripathy D, Yialamas M, Groop L, Elahi D, et al. 2005 Relationship between testosterone levels, insulin sensitivity, and mitochondrial function in men. Diabetes Care 28 1636–1642. (https://doi.org/10.2337/diacare.28.7.1636)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Rana K, Chiu MW, Russell PK, Skinner JP, Lee NK, Fam BC, Zajac JD & MacLean HE 2016 Muscle-specific androgen receptor deletion shows limited actions in myoblasts but not in myofibers in different muscles in vivo. Journal of Molecular Endocrinology 57 125–138. (https://doi.org/10.1530/JME-15-0320)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Rapizzi E, Fucci R, Giannoni E, Canu L, Richter S, Cirri P & Mannelli M 2015 Role of microenvironment on neuroblastoma SK-N-AS SDHB silenced cell metabolism and function. Endocrine-Related Cancer 22 409–417. (https://doi.org/10.1530/ERC-14-0479)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Roberts CK & Barnard RJ 2005 Effects of exercise and diet on chronic disease. Journal of Applied Physiology 98 3–30. (https://doi.org/10.1152/japplphysiol.00852.2004)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Roy TA, Blackman MR, Harman SM, Tobin JD, Schrager M & Metter EJ 2002 Interrelationships of serum testosterone and free testosterone index with FFM and strength in aging men. American Journal of Physiology: Endocrinology and Metabolism 283 E284–E294. (https://doi.org/10.1152/ajpendo.00334.2001)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Schiaffino S & Reggiani C 2011 Fiber types in mammalian skeletal muscles. Physiological Reviews 91 1447–1531. (https://doi.org/10.1152/physrev.00031.2010)

  • Shen L, Meng X, Zhang Z & Wang T 2018 Physical exercise for muscle atrophy. Advances in Experimental Medicine and Biology 1088 529–545. (https://doi.org/10.1007/978-981-13-1435-3_24)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Sinha-Hikim I, Artaza J, Woodhouse L, Gonzalez-Cadavid N, Singh AB, Lee MI, Storer TW, Casaburi R, Shen R & Bhasin S 2002 Testosterone-induced increase in muscle size in healthy young men is associated with muscle fiber hypertrophy. American Journal of Physiology: Endocrinology and Metabolism 283 E154–E164. (https://doi.org/10.1152/ajpendo.00502.2001)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Sishi B, Loos B, Ellis B, Smith W, Du Toit EF & Engelbrecht AM 2011 Diet-induced obesity alters signalling pathways and induces atrophy and apoptosis in skeletal muscle in a prediabetic rat model. Experimental Physiology 96 179–193. (https://doi.org/10.1113/expphysiol.2010.054189)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Snyder PJ, Bhasin S, Cunningham GR, Matsumoto AM, Stephens-Shields AJ, Cauley JA, Gill TM, Barrett-Connor E, Swerdloff RS, Wang C, et al. 2016 Effects of testosterone treatment in older men. New England Journal of Medicine 374 611–624. (https://doi.org/10.1056/NEJMoa1506119)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Snyder PJ, Bhasin S, Cunningham GR, Matsumoto AM, Stephens-Shields AJ, Cauley JA, Gill TM, Barrett-Connor E, Swerdloff RS, Wang C, et al. 2018 Lessons from the testosterone trials. Endocrine Reviews 39 369–386. (https://doi.org/10.1210/er.2017-00234)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Storer TW, Basaria S, Traustadottir T, Harman SM, Pencina K, Li Z, Travison TG, Miciek R, Tsitouras P, Hally K, et al. 2017 Effects of testosterone supplementation for 3 years on muscle performance and physical function in older men. Journal of Clinical Endocrinology and Metabolism 102 583–593. (https://doi.org/10.1210/jc.2016-2771)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Stuart CA, McCurry MP, Marino A, South MA, Howell ME, Layne AS, Ramsey MW & Stone MH 2013 Slow-twitch fiber proportion in skeletal muscle correlates with insulin responsiveness. Journal of Clinical Endocrinology and Metabolism 98 2027–2036. (https://doi.org/10.1210/jc.2012-3876)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Usui T, Kajita K, Kajita T, Mori I, Hanamoto T, Ikeda T, Okada H, Taguchi K, Kitada Y, Morita H, et al. 2014 Elevated mitochondrial biogenesis in skeletal muscle is associated with testosterone-induced body weight loss in male mice. FEBS Letters 588 1935–1941. (https://doi.org/10.1016/j.febslet.2014.03.051)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Wewege MA, Thom JM, Rye KA & Parmenter BJ 2018 Aerobic, resistance or combined training: a systematic review and meta-analysis of exercise to reduce cardiovascular risk in adults with metabolic syndrome. Atherosclerosis 274 162–171. (https://doi.org/10.1016/j.atherosclerosis.2018.05.002)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • White JP, Gao S, Puppa MJ, Sato S, Welle SL & Carson JA 2013 Testosterone regulation of Akt/mTORC1/FoxO3a signaling in skeletal muscle. Molecular and Cellular Endocrinology 365 174–186. (https://doi.org/10.1016/j.mce.2012.10.019)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Wu Y, Zhao W, Zhao J, Zhang Y, Qin W, Pan J, Bauman WA, Blitzer RD & Cardozo C 2010 REDD1 is a major target of testosterone action in preventing dexamethasone-induced muscle loss. Endocrinology 151 1050–1059. (https://doi.org/10.1210/en.2009-0530)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Zhang J, Phillips DI, Wang C & Byrne CD 2004 Human skeletal muscle PPARalpha expression correlates with fat metabolism gene expression but not BMI or insulin sensitivity. American Journal of Physiology: Endocrinology and Metabolism 286 E168–E175. (https://doi.org/10.1152/ajpendo.00232.2003)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Zurlo F, Larson K, Bogardus C & Ravussin E 1990 Skeletal muscle metabolism is a major determinant of resting energy expenditure. Journal of Clinical Investigation 86 1423–1427. (https://doi.org/10.1172/JCI114857)

    • PubMed
    • Search Google Scholar
    • Export Citation