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

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...

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Autores principales: Rodríguez-Rodríguez, Rosalía, Miralpeix, Cristina, Fosch, Anna, Pozo, Macarena, Calderón-Domínguez, María, Perpinyà, Xavier, Vellvehí, Miquel, López, Miguel, Herrero, Laura, Serra, Dolors, Casals, Núria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6323189/
https://www.ncbi.nlm.nih.gov/pubmed/30448371
http://dx.doi.org/10.1016/j.molmet.2018.10.010
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author Rodríguez-Rodríguez, Rosalía
Miralpeix, Cristina
Fosch, Anna
Pozo, Macarena
Calderón-Domínguez, María
Perpinyà, Xavier
Vellvehí, Miquel
López, Miguel
Herrero, Laura
Serra, Dolors
Casals, Núria
author_facet Rodríguez-Rodríguez, Rosalía
Miralpeix, Cristina
Fosch, Anna
Pozo, Macarena
Calderón-Domínguez, María
Perpinyà, Xavier
Vellvehí, Miquel
López, Miguel
Herrero, Laura
Serra, Dolors
Casals, Núria
author_sort Rodríguez-Rodríguez, Rosalía
collection PubMed
description 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.
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spelling pubmed-63231892019-01-18 CPT1C in the ventromedial nucleus of the hypothalamus is necessary for brown fat thermogenesis activation in obesity Rodríguez-Rodríguez, Rosalía Miralpeix, Cristina Fosch, Anna Pozo, Macarena Calderón-Domínguez, María Perpinyà, Xavier Vellvehí, Miquel López, Miguel Herrero, Laura Serra, Dolors Casals, Núria Mol Metab Original Article 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. Elsevier 2018-11-02 /pmc/articles/PMC6323189/ /pubmed/30448371 http://dx.doi.org/10.1016/j.molmet.2018.10.010 Text en © 2018 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Rodríguez-Rodríguez, Rosalía
Miralpeix, Cristina
Fosch, Anna
Pozo, Macarena
Calderón-Domínguez, María
Perpinyà, Xavier
Vellvehí, Miquel
López, Miguel
Herrero, Laura
Serra, Dolors
Casals, Núria
CPT1C in the ventromedial nucleus of the hypothalamus is necessary for brown fat thermogenesis activation in obesity
title CPT1C in the ventromedial nucleus of the hypothalamus is necessary for brown fat thermogenesis activation in obesity
title_full CPT1C in the ventromedial nucleus of the hypothalamus is necessary for brown fat thermogenesis activation in obesity
title_fullStr CPT1C in the ventromedial nucleus of the hypothalamus is necessary for brown fat thermogenesis activation in obesity
title_full_unstemmed CPT1C in the ventromedial nucleus of the hypothalamus is necessary for brown fat thermogenesis activation in obesity
title_short CPT1C in the ventromedial nucleus of the hypothalamus is necessary for brown fat thermogenesis activation in obesity
title_sort cpt1c in the ventromedial nucleus of the hypothalamus is necessary for brown fat thermogenesis activation in obesity
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6323189/
https://www.ncbi.nlm.nih.gov/pubmed/30448371
http://dx.doi.org/10.1016/j.molmet.2018.10.010
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