CPT1C in the ventromedial nucleus of the hypothalamus is necessary for brown fat thermogenesis activation in obesity

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-in...

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Published in:Molecular metabolism (Germany) 2019-01, Vol.19, p.75-85
Main Authors: Rodríguez-Rodríguez, Rosalía, Miralpeix, Cristina, Fosch, Anna, Pozo, Macarena, Calderón-Domínguez, María, Perpinyà, Xavier, Vellvehí, Miquel, López, Miguel, Herrero, Laura, Serra, Dolors, Casals, Núria
Format: Article
Language:English
Subjects:
Adipose Tissue, Brown - metabolism
Adipose tissues
Adiposity
Animals
Body Weight
Brown adipose tissue
Carnitina palmitoïl-transferasa 1
Carnitine O-Palmitoyltransferase - metabolism
Carnitine palmitoyltransferase I
CPT1C
Diet, High-Fat
Diet-induced obesity
Eating
Energy Metabolism
Hipotàlem
Homeostasis
Hypothalamus
Hypothalamus - metabolism
Leptin - metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Obesitat
Obesity
Obesity - metabolism
Original
Teixit adipós
Thermogenesis
Thermogenesis - physiology
Ventromedial Hypothalamic Nucleus - metabolism
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Summary: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. 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. 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. 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. •Diet- and leptin-induced thermogenesis are impaired in CPT1C KO mice.•Expression of CPT1C in the VMH restores short-term diet-induced thermogenesis in CPT1C KO mice.•AMPK inhibition in the VMH does not restore the activation of BAT in CPT1C KO mice.•CPT1C is essential in the activation of BAT thermogenesis to counteract diet-induced obesity.
ISSN:2212-8778
2212-8778
DOI:10.1016/j.molmet.2018.10.010