CPT1C in the ventromedial nucleus of the hypothalamus is necessary for brown fat thermogenesis activation in obesity
| Autor: | Rosalía Rodríguez-Rodríguez, Macarena Pozo, Laura Herrero, Cristina Miralpeix, Miquel Vellvehi, Núria Casals, Anna Fosch, Maria Calderon-Dominguez, Dolors Serra, Miguel López, Xavier Perpinya |
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| Přispěvatelé: | Universitat de Barcelona, Universidade de Santiago de Compostela. Centro de Investigación en Medicina Molecular e Enfermidades Crónicas, Universidade de Santiago de Compostela. Departamento de Fisioloxía |
| Předmět: |
Leptin
Male 0301 basic medicine Termometria Obesidad Termometría Brown adipose tissue Energy homeostasis Eating Mice 0302 clinical medicine Adipose Tissue Brown CPT1C Homeostasis Adiposity Mice Knockout Hipotàlem Carnitina palmitoïl-transferasa 1 Diet-induced obesity Thermogenesis Ventromedial nucleus of the hypothalamus medicine.anatomical_structure Hypothalamus Obesitat Tejido adiposo medicine.medical_specialty 030209 endocrinology & metabolism Biology Diet High-Fat 03 medical and health sciences Internal medicine medicine Animals Obesity Molecular Biology Carnitine O-Palmitoyltransferase Body Weight Wild type AMPK Adipose tissues Cell Biology Mice Inbred C57BL Teixit adipós 030104 developmental biology Endocrinology Ventromedial Hypothalamic Nucleus Carnitine palmitoyltransferase I Energy Metabolism Hipotálamo |
| Zdroj: | Recercat. Dipósit de la Recerca de Catalunya instname Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela Dipòsit Digital de la UB Universidad de Barcelona Recercat: Dipósit de la Recerca de Catalunya Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Popis: | Objective:Carnitine palmitoyltransferase 1C (CPT1C) is implicated in central regulation of energy homeostasis. Our aim was to investigatewhether CPT1C in the ventromedial nucleus of the hypothalamus (VMH) is involved in the activation of brown adipose tissue (BAT) thermogenesisin the early stages of diet-induced obesity.Methods:CPT1C KO and wild type (WT) mice were exposed to short-term high-fat (HF) diet feeding or to intracerebroventricular leptinadministration and BAT thermogenesis activation was evaluated. Body weight, adiposity, food intake, and leptinemia were also assayed.Results:Under 7 days of HF diet, WT mice showed a maximum activation peak of BAT thermogenesis that counteracted obesity development,whereas this activation was impaired in CPT1C KO mice. KO animals evidenced higher body weight, adiposity, hyperleptinemia, ER stress, anddisrupted hypothalamic leptin signaling. Leptin-induced BAT thermogenesis was abolished in KO mice. These results indicate an earlier onsetleptin resistance in CPT1C KO mice. Since AMPK in the VMH is crucial in the regulation of BAT thermogenesis, we analyzed if CPT1C was adownstream factor of this pathway. Genetic inactivation of AMPK within the VMH was unable to induce BAT thermogenesis and body weight lossin KO mice, indicating that CPT1C is likely downstream AMPK in the central mechanism modulating thermogenesis within the VMH. Quiteopposite, the expression of CPT1C in the VMH restored the phenotype.Conclusion:CPT1C is necessary for the activation of BAT thermogenesis driven by leptin, HF diet exposure, and AMPK inhibition within the VMH.This study underscores the importance of CPT1C in the activation of BAT thermogenesis to counteract diet-induced obesity This work was supported by the Ministerio de Economía, Industria y Competitividad (MINECO), Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER) (Grants SAF2014-52223-C2-2-R to NC, SAF2017-83813-C3-3-R to NC and RR-R, SAF2014-52223-C2-1-R to DS, SAF2017-83813-C3-1-R to DS and LH, SAF2015-71026-R to ML, TEC2014-51903-R to MV and XP, and Ramón y Cajal RYC-2010-07434 to XP), the Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y la Nutrición (CIBEROBN) (Grant CB06/03/0001 to DS), the Generalitat de Catalunya (2014SGR465 to DS and NC, 2017SGR1384 to MV and XP), Fundació La Marató de TV3 (Grant 87/C/2016 to DS and NC), and by Projectes de Recerca per a investigadors novells (2015) to RR-R. AF is the recipient of a fellowship from the Agència de Gestió d’Ajuts Universitaris i de la Recerca (AGAUR) in Catalonia SI |
| Databáze: | OpenAIRE |
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