The corticotrophin-releasing factor/urocortin system regulates white fat browning in mice through paracrine mechanisms
| Autor: | Yolanda Diz-Chaves, Danijela Markovic, Dimitris K. Grammatopoulos, Flaminia Fanelli, Angelo Contarino, Daniela Cota, Luc Pénicaud, Antoine Tabarin, Samantha Clark, Hendrik Lehnert, Buyu Lu |
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| Přispěvatelé: | University of Warwick [Coventry], Institut de Neurosciences Cognitives et Intégratives d’Aquitaine ( INCIA ), Université de Bordeaux ( UB ), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Università di Bologna [Bologna] ( UNIBO ), Institut National de la Santé et de la Recherche Médicale, University of Luebeck, Lu B, Diz-Chaves Y, Markovic D, Contarino A, Penicaud L, Fanelli F, Clark S, Lehnert H, Cota D, Grammatopoulos DK, Tabarin A, Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Università di Bologna [Bologna] (UNIBO), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO) |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
obesity
crf1 Corticotropin-Releasing Hormone crf2 Endocrinology Diabetes and Metabolism IMPAIRED STRESS-RESPONSE [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition Adipocytes White Medicine (miscellaneous) urocortin White adipose tissue MOUSE Mice brown adiposte tissue 0302 clinical medicine Browning Urocortins Urocortin 0303 health sciences Nutrition and Dietetics [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism Paracrine mechanisms [ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism Immunohistochemistry ADIPOCYTES Adipocytes Brown ADIPOSE-TISSUE SKELETAL-MUSCLE hormones hormone substitutes and hormone antagonists Signal Transduction EXPRESSION medicine.medical_specialty endocrine system THERMOGENESIS Biology crf Receptors Corticotropin-Releasing Hormone 03 medical and health sciences white adipose tissue Internal medicine 3T3-L1 Cells medicine Animals RNA Messenger GLUCOCORTICOIDS 030304 developmental biology ENERGY HOMEOSTASIS Corticotrophin releasing factor adipose plasticity Pigments Biological UROCORTIN-II GENE QP Endocrinology Gene Expression Regulation [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition 030217 neurology & neurosurgery |
| Zdroj: | International journal of obesity (2005) International journal of obesity (2005), 2015, 39 (3), pp.408-17. 〈10.1038/ijo.2014.164〉 International journal of obesity (2005), 2015, 39 (3), pp.408-17. ⟨10.1038/ijo.2014.164⟩ |
| ISSN: | 1476-5497 0307-0565 |
| DOI: | 10.1038/ijo.2014.164〉 |
| Popis: | Objectives:\ud The corticotrophin-releasing factor (CRF)/urocortin system is expressed in the adipose tissue of mammals, but its functional role in this tissue remains unknown.\ud \ud Methods:\ud Pharmacological manipulation of the activity of CRF receptors, CRF1 and CRF2, was performed in 3T3L1 white pre-adipocytes and T37i brown pre-adipocytes during in vitro differentiation. The expression of genes of the CRF/urocortin system and of markers of white and brown adipocytes was evaluated along with mitochondrial biogenesis and cellular oxygen consumption. Metabolic evaluation of corticosterone-deficient or supplemented Crhr1-null (Crhr1−/−) mice and their wild-type controls was performed along with gene expression analysis carried out in white (WAT) and brown (BAT) adipose tissues.\ud \ud Results:\ud Peptides of the CRF/urocortin system and their cognate receptors were expressed in both pre-adipocyte cell lines. In vitro pharmacological studies showed an inhibition of the expression of the CRF2 pathway by the constitutive activity of the CRF1 pathway. Pharmacological activation of CRF2 and, to a lesser extent, inhibition of CRF1 signaling induced molecular and functional changes indicating transdifferentiation of white pre-adipocytes and differentiation of brown pre-adipocytes. Crhr1−/− mice showed increased expression of CRF2 and its agonist Urocortin 2 in adipocytes that was associated to brown conversion of WAT and activation of BAT. Crhr1−/− mice were resistant to diet-induced obesity and glucose intolerance. Restoring physiological circulating corticosterone levels abrogated molecular changes in adipocytes and the favorable phenotype of Crhr1−/− mice.\ud \ud Conclusions:\ud Our findings suggest the importance of the CRF2 pathway in the control of adipocyte plasticity. Increased CRF2 activity in adipocytes induces browning of WAT, differentiation of BAT and is associated with a favorable metabolic phenotype in mice lacking CRF1. Circulating corticosterone represses CRF2 activity in adipocytes and may thus regulate adipocyte physiology through the modulation of the local CRF/urocortin system. Targeting CRF receptor signaling specifically in the adipose tissue may represent a novel approach to tackle obesity. |
| Databáze: | OpenAIRE |
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