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Title: CPT1C in the ventromedial nucleus of the hypothalamus is necessary for brown fat thermogenesis activation in obesity
Author: Rodríguez-Rodríguez, Rosalía
Miralpeix, Cristina
Fosch, Anna
Pozo, Macarena
Calderón Domínguez, María
Perpinyà, Xavier
Vellvehí, Miquel
López, Miguel
Herrero Rodríguez, Laura
Serra i Cucurull, Dolors
Casals i Farré, Núria
Keywords: Carnitina palmitoïl-transferasa 1
Teixit adipós
Carnitine palmitoyltransferase I
Adipose tissues
Issue Date: 2-Nov-2018
Publisher: Elsevier GmbH
Abstract: OBJECTIVE: Carnitine palmitoyltransferase 1C (CPT1C) is implicated in central regulation of energy homeostasis. Our aim was to investigate whether CPT1C in the ventromedial nucleus of the hypothalamus (VMH) is involved in the activation of brown adipose tissue (BAT) thermogenesis in 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 leptin administration 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, and disrupted hypothalamic leptin signaling. Leptin-induced BAT thermogenesis was abolished in KO mice. These results indicate an earlier onset leptin resistance in CPT1C KO mice. Since AMPK in the VMH is crucial in the regulation of BAT thermogenesis, we analyzed if CPT1C was a downstream factor of this pathway. Genetic inactivation of AMPK within the VMH was unable to induce BAT thermogenesis and body weight loss in KO mice, indicating that CPT1C is likely downstream AMPK in the central mechanism modulating thermogenesis within the VMH. Quite opposite, 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. Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved. KEYWORDS: Brown adipose tissue; CPT1C; Diet-induced obesity; Hypothalamus; Thermogenesis
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It is part of: Molecular Metabolism, 2018, vol. 2019, num. 19, p. 75-85
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ISSN: 2212-8778
Appears in Collections:Articles publicats en revistes (Bioquímica i Fisiologia)
Articles publicats en revistes (Institut de Biomedicina (IBUB))

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