CPT1C in the ventromedial nucleus of the hypothalamus is necessary for brown fat thermogenesis activation in obesity
Molecular Metabolism. 2019-01-01; 19: 75-85
DOI: 10.1016/j.molmet.2018.10.010
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Rodríguez-Rodríguez R(1), Miralpeix C(2), Fosch A(2), Pozo M(2), Calderón-Domínguez M(3), Perpinyà X(4), Vellvehí M(4), López M(5), Herrero L(6),
Serra D(6), Casals N(7).
Author information:
(1)Basic Sciences Department, Faculty of Medicine and Health Sciences,
Universitat Internacional de Catalunya, 08195, Sant Cugat del Vallès, Spain.
Electronic address: .
(2)Basic Sciences Department, Faculty of Medicine and Health Sciences,
Universitat Internacional de Catalunya, 08195, Sant Cugat del Vallès, Spain.
(3)Department of Biochemistry and Physiology, School of Pharmacy, Institut de
Biomedicina de la Universitat de Barcelona (IBUB), Universitat de Barcelona,
E-08028, Barcelona, Spain.
(4)Instituto de Microelectrónica de Barcelona (IMB-CNM, CSIC), Campus UAB, 08193,
Cerdanyola del Vallès (Bellaterra), Spain.
(5)NeurObesity Group, Department of Physiology, CIMUS, University of Santiago de
Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782,
Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad
y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, E-28029, Madrid, Spain.
(6)Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la
Nutrición (CIBEROBN), Instituto de Salud Carlos III, E-28029, Madrid, Spain;
Department of Biochemistry and Physiology, School of Pharmacy, Institut de
Biomedicina de la Universitat de Barcelona (IBUB), Universitat de Barcelona,
E-08028, Barcelona, Spain.
(7)Basic Sciences Department, Faculty of Medicine and Health Sciences,
Universitat Internacional de Catalunya, 08195, Sant Cugat del Vallès, Spain;
Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la
Nutrición (CIBEROBN), Instituto de Salud Carlos III, E-28029, Madrid, Spain.
Electronic address: .
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.