Search Results
You are looking at 1 - 6 of 6 items for
- Author: Carlos Diéguez x
- Refine by access: All content x
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain
Search for other papers by Noelia Martínez-Sánchez in
Google Scholar
PubMed
Department of Diabetes, Endocrinology and Nutrition, Hospital de Girona ‘Dr Josep Trueta’, Institut D’investigació Biomèdica de Girona (IdIBGi) and University of Girona, Girona, Spain
Search for other papers by José M Moreno-Navarrete in
Google Scholar
PubMed
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain
Search for other papers by Cristina Contreras in
Google Scholar
PubMed
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain
Search for other papers by Eva Rial-Pensado in
Google Scholar
PubMed
Department of Clinical Science, KG Jebsen Center for Diabetes Research, University of Bergen, Bergen, Norway
Search for other papers by Johan Fernø in
Google Scholar
PubMed
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain
Search for other papers by Rubén Nogueiras in
Google Scholar
PubMed
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain
Search for other papers by Carlos Diéguez in
Google Scholar
PubMed
Department of Diabetes, Endocrinology and Nutrition, Hospital de Girona ‘Dr Josep Trueta’, Institut D’investigació Biomèdica de Girona (IdIBGi) and University of Girona, Girona, Spain
Search for other papers by José-Manuel Fernández-Real in
Google Scholar
PubMed
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain
Search for other papers by Miguel López in
Google Scholar
PubMed
The canonical view about the effect of thyroid hormones (THs) on thermogenesis assumes that the hypothalamus acts merely as a modulator of the sympathetic outflow on brown adipose tissue (BAT). Recent data have challenged that vision by demonstrating that THs act on the ventromedial nucleus of the hypothalamus (VMH) to inhibit AMP-activated protein kinase (AMPK), which regulates the thermogenic program in BAT, leading to increased thermogenesis and weight loss. Current data have shown that in addition to activation of brown fat, the browning of white adipose tissue (WAT) might also be an important thermogenic mechanism. However, the possible central effects of THs on the browning of white fat remain unclear. Here, we show that 3,3′,5,5′ tetraiodothyroxyne (T4)-induced hyperthyroidism promotes a marked browning of WAT. Of note, central or VMH-specific administration of 3,3′,5-triiodothyronine (T3) recapitulates that effect. The specific genetic activation of hypothalamic AMPK in the VMH reversed the central effect of T3 on browning. Finally, we also showed that the expression of browning genes in human WAT correlates with serum T4. Overall, these data indicate that THs induce browning of WAT and that this mechanism is mediated via the central effects of THs on energy balance.
Obesity and Metabolic Health Division, Rowett Research Institute, Aberdeen AB21 9SB, UK
Search for other papers by Ruben Nogueiras in
Google Scholar
PubMed
Obesity and Metabolic Health Division, Rowett Research Institute, Aberdeen AB21 9SB, UK
Search for other papers by Sulay Tovar in
Google Scholar
PubMed
Obesity and Metabolic Health Division, Rowett Research Institute, Aberdeen AB21 9SB, UK
Search for other papers by Sharon E Mitchell in
Google Scholar
PubMed
Obesity and Metabolic Health Division, Rowett Research Institute, Aberdeen AB21 9SB, UK
Search for other papers by Perry Barrett in
Google Scholar
PubMed
Obesity and Metabolic Health Division, Rowett Research Institute, Aberdeen AB21 9SB, UK
Search for other papers by D Vernon Rayner in
Google Scholar
PubMed
Obesity and Metabolic Health Division, Rowett Research Institute, Aberdeen AB21 9SB, UK
Search for other papers by Carlos Dieguez in
Google Scholar
PubMed
Obesity and Metabolic Health Division, Rowett Research Institute, Aberdeen AB21 9SB, UK
Search for other papers by Lynda M Williams in
Google Scholar
PubMed
Central neuromedin U (NMU) functions in energy balance, the hypothalamic–pituitary–adrenal axis, LH release and circadian rhythmicity. In rats, high levels of NMU occur in the hypothalamic suprachiasmatic nuclei and the pars tuberalis of the pituitary. NMU expression in the pars tuberalis appears to be downregulated in the Zucker fatty (fa/fa) rat, lacking functional leptin receptors. In contrast, in the dorsomedial (DMH) nuclei of the mouse, NMU expression is higher in the ob/ob mouse, lacking leptin, and is upregulated by fasting. However, leptin appears not to change NMU gene expression in either the mouse DMH or the rat pars tuberalis. Thus, the present study aims to better identify factors influencing central NMU expression in the rat pars tuberalis. Sprague–Dawley rats were fasted and/or challenged with intracerebroventricular leptin or ghrelin and gene expression was measured using real-time reverse transcriptase-PCR and quantitative in situ hybridisation with riboprobes specific for NMU and NMU receptor (NMU-R2). NMU expression in the rat pars tuberalis was elevated by fasting. Ghrelin administration had no effect on the level of NMU expression, but leptin was found to diminish the expression in a concentration- and time-dependent manner. NMU-R2 expression was unchanged in any of the groups measured. These results suggest that NMU expression in rat pars tuberalis is upregulated in states of negative energy balance, and this may be mediated indirectly by changes in leptin levels. These results demonstrate a link between energy balance and NMU expression in the pars tuberalis of the pituitary.
Department of Physiology, University of Santiago de Compostela, 15705 Santiago de Compostela, Spain
Search for other papers by Sharon E Mitchell in
Google Scholar
PubMed
Department of Physiology, University of Santiago de Compostela, 15705 Santiago de Compostela, Spain
Search for other papers by Ruben Nogueiras in
Google Scholar
PubMed
Department of Physiology, University of Santiago de Compostela, 15705 Santiago de Compostela, Spain
Search for other papers by Kellie Rance in
Google Scholar
PubMed
Department of Physiology, University of Santiago de Compostela, 15705 Santiago de Compostela, Spain
Search for other papers by D Vernon Rayner in
Google Scholar
PubMed
Department of Physiology, University of Santiago de Compostela, 15705 Santiago de Compostela, Spain
Search for other papers by Sharon Wood in
Google Scholar
PubMed
Department of Physiology, University of Santiago de Compostela, 15705 Santiago de Compostela, Spain
Search for other papers by Carlos Dieguez in
Google Scholar
PubMed
Department of Physiology, University of Santiago de Compostela, 15705 Santiago de Compostela, Spain
Search for other papers by Lynda M Williams in
Google Scholar
PubMed
To ascertain the mechanisms underlying low caloric intake and low body weight in the Lou/C rat, the circulating hormone levels and gene expression of hypothalamic peptides and receptors important in energy balance and the induction of suppressor of cytokine signalling 3 (SOCS3) gene expression in response to leptin challenge were compared with Wistar rats. Plasma leptin levels were lower in the Lou/C rat, as were levels of rat corticosterone, TSH and T4 but not T3. Ghrelin levels were higher in the Lou/C rat. Total leptin receptor (Ob-R) and the long form of the leptin receptor (Ob-Rb) gene expression were lower in the arcuate (ARC) and ventromedial nuclei (VMN) in Lou/C rat. Ghrelin receptor expression in the ARC and VMN was lower in Lou/C than in Wistar rats. However, agouti gene-related peptide (AgRP) and neuropeptide Y (NPY) gene expression were higher in the Lou/C rat. There was no difference in the level of cocaine- and amphetamine-regulated transcript gene expression in the ARC, but both were higher in the paraventricular nuclei of the Lou/C breed. There was no difference in Ob-R gene expression in, or [125I]leptin binding to, the choroid plexus. SOCS3 mRNA induction in response to leptin was lower in the Lou/C rat. This study reveals that the comparatively low plasma leptin, TSH and T4 levels, and high ghrelin levels together with high levels of AgRP and NPY gene expression seen in the Lou/C rat are indicative of a strong drive to eat and decreased energy expenditure, which are in direct opposition to the comparatively low body weight and adiposity of this rat strain.
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain
Search for other papers by Ismael González-García in
Google Scholar
PubMed
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain
Search for other papers by Pablo B Martínez de Morentin in
Google Scholar
PubMed
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain
Search for other papers by Ánxela Estévez-Salguero in
Google Scholar
PubMed
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain
Search for other papers by Cristina Contreras in
Google Scholar
PubMed
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain
Search for other papers by Amparo Romero-Picó in
Google Scholar
PubMed
KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway
Search for other papers by Johan Fernø in
Google Scholar
PubMed
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain
Search for other papers by Rubén Nogueiras in
Google Scholar
PubMed
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain
Search for other papers by Carlos Diéguez in
Google Scholar
PubMed
Instituto Maimónides de Investigación Biomédica (IMIBIC)/Hospital Reina Sofía, Córdoba, Spain
FiDiPro Program, University of Turku, Turku, Finland
Search for other papers by Manuel Tena-Sempere in
Google Scholar
PubMed
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain
Search for other papers by Sulay Tovar in
Google Scholar
PubMed
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain
Search for other papers by Miguel López in
Google Scholar
PubMed
Current evidence suggests that estradiol (E2), the main ovarian steroid, modulates energy balance by regulating both feeding and energy expenditure at the central level, through the energy sensor AMP-activated protein kinase (AMPK). We hypothesized that the hypothalamic mechanistic target of rapamycin (mTOR) pathway, a well-established nutrient sensor and modulator of appetite and puberty, could also mediate the anorectic effect of E2. Our data showed that ovariectomy (OVX) elicited a marked downregulation of the mTOR signaling in the arcuate nucleus of the hypothalamus (ARC), an effect that was reversed by either E2 replacement or central estrogen receptor alpha (ERα) agonism. The significance of this molecular signaling was given by the genetic inactivation of S6 kinase B1 (S6K1, a key downstream mTOR effector) in the ARC, which prevented the E2-induced hypophagia and weight loss. Overall, these data indicate that E2 induces hypophagia through modulation of mTOR pathway in the ARC.
Fundación IMABIS, Instituto de Bioingeniería and CIBER de Diabetes y Enfermedades Metabólicas asociadas (CIBERDEM), Department of Physiology, CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Institute of Medical Sciences, Neurocentre Magendie, Hospital Carlos Haya de Málaga, Laboratorio de Medicina Regenerativa, Pabellón de Gobierno, sótano, Avenida Carlos Haya 82, 29010 Málaga, Spain
Search for other papers by Silvana Y Romero-Zerbo in
Google Scholar
PubMed
Search for other papers by Alex Rafacho in
Google Scholar
PubMed
Fundación IMABIS, Instituto de Bioingeniería and CIBER de Diabetes y Enfermedades Metabólicas asociadas (CIBERDEM), Department of Physiology, CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Institute of Medical Sciences, Neurocentre Magendie, Hospital Carlos Haya de Málaga, Laboratorio de Medicina Regenerativa, Pabellón de Gobierno, sótano, Avenida Carlos Haya 82, 29010 Málaga, Spain
Search for other papers by Adenis Díaz-Arteaga in
Google Scholar
PubMed
Fundación IMABIS, Instituto de Bioingeniería and CIBER de Diabetes y Enfermedades Metabólicas asociadas (CIBERDEM), Department of Physiology, CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Institute of Medical Sciences, Neurocentre Magendie, Hospital Carlos Haya de Málaga, Laboratorio de Medicina Regenerativa, Pabellón de Gobierno, sótano, Avenida Carlos Haya 82, 29010 Málaga, Spain
Search for other papers by Juan Suárez in
Google Scholar
PubMed
Search for other papers by Ivan Quesada in
Google Scholar
PubMed
Fundación IMABIS, Instituto de Bioingeniería and CIBER de Diabetes y Enfermedades Metabólicas asociadas (CIBERDEM), Department of Physiology, CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Institute of Medical Sciences, Neurocentre Magendie, Hospital Carlos Haya de Málaga, Laboratorio de Medicina Regenerativa, Pabellón de Gobierno, sótano, Avenida Carlos Haya 82, 29010 Málaga, Spain
Search for other papers by Mónica Imbernon in
Google Scholar
PubMed
Search for other papers by Ruth A Ross in
Google Scholar
PubMed
Fundación IMABIS, Instituto de Bioingeniería and CIBER de Diabetes y Enfermedades Metabólicas asociadas (CIBERDEM), Department of Physiology, CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Institute of Medical Sciences, Neurocentre Magendie, Hospital Carlos Haya de Málaga, Laboratorio de Medicina Regenerativa, Pabellón de Gobierno, sótano, Avenida Carlos Haya 82, 29010 Málaga, Spain
Search for other papers by Carlos Dieguez in
Google Scholar
PubMed
Fundación IMABIS, Instituto de Bioingeniería and CIBER de Diabetes y Enfermedades Metabólicas asociadas (CIBERDEM), Department of Physiology, CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Institute of Medical Sciences, Neurocentre Magendie, Hospital Carlos Haya de Málaga, Laboratorio de Medicina Regenerativa, Pabellón de Gobierno, sótano, Avenida Carlos Haya 82, 29010 Málaga, Spain
Search for other papers by Fernando Rodríguez de Fonseca in
Google Scholar
PubMed
Fundación IMABIS, Instituto de Bioingeniería and CIBER de Diabetes y Enfermedades Metabólicas asociadas (CIBERDEM), Department of Physiology, CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Institute of Medical Sciences, Neurocentre Magendie, Hospital Carlos Haya de Málaga, Laboratorio de Medicina Regenerativa, Pabellón de Gobierno, sótano, Avenida Carlos Haya 82, 29010 Málaga, Spain
Search for other papers by Rubén Nogueiras in
Google Scholar
PubMed
Search for other papers by Ángel Nadal in
Google Scholar
PubMed
Fundación IMABIS, Instituto de Bioingeniería and CIBER de Diabetes y Enfermedades Metabólicas asociadas (CIBERDEM), Department of Physiology, CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Institute of Medical Sciences, Neurocentre Magendie, Hospital Carlos Haya de Málaga, Laboratorio de Medicina Regenerativa, Pabellón de Gobierno, sótano, Avenida Carlos Haya 82, 29010 Málaga, Spain
Fundación IMABIS, Instituto de Bioingeniería and CIBER de Diabetes y Enfermedades Metabólicas asociadas (CIBERDEM), Department of Physiology, CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Institute of Medical Sciences, Neurocentre Magendie, Hospital Carlos Haya de Málaga, Laboratorio de Medicina Regenerativa, Pabellón de Gobierno, sótano, Avenida Carlos Haya 82, 29010 Málaga, Spain
Search for other papers by Francisco J Bermúdez-Silva in
Google Scholar
PubMed
The cannabinoid CB1 receptor is a well-known player in energy homeostasis and its specific antagonism has been used in clinical practice for the treatment of obesity. The G protein-coupled receptor GPR55 has been recently proposed as a new cannabinoid receptor and, by contrast, its pharmacology is still enigmatic and its physiological role is largely unexplored, with no reports investigating its putative role in metabolism. Thus, we aim to investigate in rats the presence, distribution and putative physiological role of GPR55 in a key metabolic tissue, the endocrine pancreas. We found high Gpr55 mRNA content in pancreatic islets and considerable protein distribution in insulin-secreting β-cells. Activation of GPR55 by the agonist O-1602 increased calcium transients (P<0.01) and insulin secretion (P<0.001) stimulated by glucose. This latter effect was blunted in Gpr55 KO mice suggesting that O-1602 is acting, at least in part, through GPR55. Indeed, acute in vivo experiments showed that GPR55 activation increases glucose tolerance (P<0.05) and plasma insulin levels (P<0.05), suggesting an in vivo physiological relevance of GPR55 systemic stimulation. Taken together, these results reveal the expression of GPR55 receptors in the endocrine pancreas as well as its function at stimulus-secretion coupling of insulin secretion, suggesting a role in glucose homeostasis. In this context, it may also represent a new target for consideration in the management of type 2 diabetes and related diseases.
Instituto de Biología Molecular y Celular del Cáncer, CSIC-University of Salamanca, Salamanca, Spain
Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), CSIC-University of Salamanca, Salamanca, Spain
Search for other papers by L Francisco Lorenzo-Martín in
Google Scholar
PubMed
Instituto de Biología Molecular y Celular del Cáncer, CSIC-University of Salamanca, Salamanca, Spain
Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), CSIC-University of Salamanca, Salamanca, Spain
Search for other papers by Mauricio Menacho-Márquez in
Google Scholar
PubMed
Instituto de Biología Molecular y Celular del Cáncer, CSIC-University of Salamanca, Salamanca, Spain
Search for other papers by Salvatore Fabbiano in
Google Scholar
PubMed
Centro de Investigación en Medicina Molecular e Enfermidades Crónicas, University of Santiago de Compostela, Santiago de Compostela, Spain
Centro de Investigación Biomédica en Red de Cáncer sobre la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), University of Santiago de Compostela, Santiago de Compostela, Spain
Search for other papers by Omar Al-Massadi in
Google Scholar
PubMed
Instituto de Biología Molecular y Celular del Cáncer, CSIC-University of Salamanca, Salamanca, Spain
Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), CSIC-University of Salamanca, Salamanca, Spain
Search for other papers by Antonio Abad in
Google Scholar
PubMed
Instituto de Biología Molecular y Celular del Cáncer, CSIC-University of Salamanca, Salamanca, Spain
Search for other papers by Sonia Rodríguez-Fdez in
Google Scholar
PubMed
Instituto de Biología Molecular y Celular del Cáncer, CSIC-University of Salamanca, Salamanca, Spain
Search for other papers by María A Sevilla in
Google Scholar
PubMed
Instituto de Biología Molecular y Celular del Cáncer, CSIC-University of Salamanca, Salamanca, Spain
Search for other papers by María J Montero in
Google Scholar
PubMed
Centro de Investigación en Medicina Molecular e Enfermidades Crónicas, University of Santiago de Compostela, Santiago de Compostela, Spain
Centro de Investigación Biomédica en Red de Cáncer sobre la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), University of Santiago de Compostela, Santiago de Compostela, Spain
Search for other papers by Carlos Diéguez in
Google Scholar
PubMed
Centro de Investigación en Medicina Molecular e Enfermidades Crónicas, University of Santiago de Compostela, Santiago de Compostela, Spain
Centro de Investigación Biomédica en Red de Cáncer sobre la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), University of Santiago de Compostela, Santiago de Compostela, Spain
Search for other papers by Rubén Nogueiras in
Google Scholar
PubMed
Instituto de Biología Molecular y Celular del Cáncer, CSIC-University of Salamanca, Salamanca, Spain
Search for other papers by Xosé R Bustelo in
Google Scholar
PubMed
Multiple crosstalk between peripheral organs and the nervous system are required to maintain physiological and metabolic homeostasis. Using Vav3-deficient mice as a model for chronic sympathoexcitation-associated disorders, we report here that afferent fibers of the hepatic branch of the vagus nerve are needed for the development of the peripheral sympathoexcitation, tachycardia, tachypnea, insulin resistance, liver steatosis and adipose tissue thermogenesis present in those mice. This neuronal pathway contributes to proper activity of the rostral ventrolateral medulla, a sympathoregulatory brainstem center hyperactive in Vav3−/− mice. Vagal afferent inputs are also required for the development of additional pathophysiological conditions associated with deregulated rostral ventrolateral medulla activity. By contrast, they are dispensable for other peripheral sympathoexcitation-associated disorders sparing metabolic alterations in liver.
