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Long-Term Increased Carnitine Palmitoyltransferase 1A Expression in Ventromedial Hypotalamus Causes Hyperphagia and Alters the Hypothalamic Lipidomic Profile
Lipid metabolism in the ventromedial hypothalamus (VMH) has emerged as a crucial pathway in the regulation of feeding and energy homeostasis. Carnitine palmitoyltransferase (CPT) 1A is the rate-limiting enzyme in mitochondrial fatty acid β-oxidation and it has been proposed as a crucial mediator of...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4018328/ https://www.ncbi.nlm.nih.gov/pubmed/24819600 http://dx.doi.org/10.1371/journal.pone.0097195 |
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author | Mera, Paula Mir, Joan Francesc Fabriàs, Gemma Casas, Josefina Costa, Ana S. H. Malandrino, Maria Ida Fernández-López, José-Antonio Remesar, Xavier Gao, Su Chohnan, Shigeru Rodríguez-Peña, Maria Sol Petry, Harald Asins, Guillermina Hegardt, Fausto G. Herrero, Laura Serra, Dolors |
author_facet | Mera, Paula Mir, Joan Francesc Fabriàs, Gemma Casas, Josefina Costa, Ana S. H. Malandrino, Maria Ida Fernández-López, José-Antonio Remesar, Xavier Gao, Su Chohnan, Shigeru Rodríguez-Peña, Maria Sol Petry, Harald Asins, Guillermina Hegardt, Fausto G. Herrero, Laura Serra, Dolors |
author_sort | Mera, Paula |
collection | PubMed |
description | Lipid metabolism in the ventromedial hypothalamus (VMH) has emerged as a crucial pathway in the regulation of feeding and energy homeostasis. Carnitine palmitoyltransferase (CPT) 1A is the rate-limiting enzyme in mitochondrial fatty acid β-oxidation and it has been proposed as a crucial mediator of fasting and ghrelin orexigenic signalling. However, the relationship between changes in CPT1A activity and the intracellular downstream effectors in the VMH that contribute to appetite modulation is not fully understood. To this end, we examined the effect of long-term expression of a permanently activated CPT1A isoform by using an adeno-associated viral vector injected into the VMH of rats. Peripherally, this procedure provoked hyperghrelinemia and hyperphagia, which led to overweight, hyperglycemia and insulin resistance. In the mediobasal hypothalamus (MBH), long-term CPT1AM expression in the VMH did not modify acyl-CoA or malonyl-CoA levels. However, it altered the MBH lipidomic profile since ceramides and sphingolipids increased and phospholipids decreased. Furthermore, we detected increased vesicular γ-aminobutyric acid transporter (VGAT) and reduced vesicular glutamate transporter 2 (VGLUT2) expressions, both transporters involved in this orexigenic signal. Taken together, these observations indicate that CPT1A contributes to the regulation of feeding by modulating the expression of neurotransmitter transporters and lipid components that influence the orexigenic pathways in VMH. |
format | Online Article Text |
id | pubmed-4018328 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-40183282014-05-16 Long-Term Increased Carnitine Palmitoyltransferase 1A Expression in Ventromedial Hypotalamus Causes Hyperphagia and Alters the Hypothalamic Lipidomic Profile Mera, Paula Mir, Joan Francesc Fabriàs, Gemma Casas, Josefina Costa, Ana S. H. Malandrino, Maria Ida Fernández-López, José-Antonio Remesar, Xavier Gao, Su Chohnan, Shigeru Rodríguez-Peña, Maria Sol Petry, Harald Asins, Guillermina Hegardt, Fausto G. Herrero, Laura Serra, Dolors PLoS One Research Article Lipid metabolism in the ventromedial hypothalamus (VMH) has emerged as a crucial pathway in the regulation of feeding and energy homeostasis. Carnitine palmitoyltransferase (CPT) 1A is the rate-limiting enzyme in mitochondrial fatty acid β-oxidation and it has been proposed as a crucial mediator of fasting and ghrelin orexigenic signalling. However, the relationship between changes in CPT1A activity and the intracellular downstream effectors in the VMH that contribute to appetite modulation is not fully understood. To this end, we examined the effect of long-term expression of a permanently activated CPT1A isoform by using an adeno-associated viral vector injected into the VMH of rats. Peripherally, this procedure provoked hyperghrelinemia and hyperphagia, which led to overweight, hyperglycemia and insulin resistance. In the mediobasal hypothalamus (MBH), long-term CPT1AM expression in the VMH did not modify acyl-CoA or malonyl-CoA levels. However, it altered the MBH lipidomic profile since ceramides and sphingolipids increased and phospholipids decreased. Furthermore, we detected increased vesicular γ-aminobutyric acid transporter (VGAT) and reduced vesicular glutamate transporter 2 (VGLUT2) expressions, both transporters involved in this orexigenic signal. Taken together, these observations indicate that CPT1A contributes to the regulation of feeding by modulating the expression of neurotransmitter transporters and lipid components that influence the orexigenic pathways in VMH. Public Library of Science 2014-05-12 /pmc/articles/PMC4018328/ /pubmed/24819600 http://dx.doi.org/10.1371/journal.pone.0097195 Text en © 2014 Mera et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Mera, Paula Mir, Joan Francesc Fabriàs, Gemma Casas, Josefina Costa, Ana S. H. Malandrino, Maria Ida Fernández-López, José-Antonio Remesar, Xavier Gao, Su Chohnan, Shigeru Rodríguez-Peña, Maria Sol Petry, Harald Asins, Guillermina Hegardt, Fausto G. Herrero, Laura Serra, Dolors Long-Term Increased Carnitine Palmitoyltransferase 1A Expression in Ventromedial Hypotalamus Causes Hyperphagia and Alters the Hypothalamic Lipidomic Profile |
title | Long-Term Increased Carnitine Palmitoyltransferase 1A Expression in Ventromedial Hypotalamus Causes Hyperphagia and Alters the Hypothalamic Lipidomic Profile |
title_full | Long-Term Increased Carnitine Palmitoyltransferase 1A Expression in Ventromedial Hypotalamus Causes Hyperphagia and Alters the Hypothalamic Lipidomic Profile |
title_fullStr | Long-Term Increased Carnitine Palmitoyltransferase 1A Expression in Ventromedial Hypotalamus Causes Hyperphagia and Alters the Hypothalamic Lipidomic Profile |
title_full_unstemmed | Long-Term Increased Carnitine Palmitoyltransferase 1A Expression in Ventromedial Hypotalamus Causes Hyperphagia and Alters the Hypothalamic Lipidomic Profile |
title_short | Long-Term Increased Carnitine Palmitoyltransferase 1A Expression in Ventromedial Hypotalamus Causes Hyperphagia and Alters the Hypothalamic Lipidomic Profile |
title_sort | long-term increased carnitine palmitoyltransferase 1a expression in ventromedial hypotalamus causes hyperphagia and alters the hypothalamic lipidomic profile |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4018328/ https://www.ncbi.nlm.nih.gov/pubmed/24819600 http://dx.doi.org/10.1371/journal.pone.0097195 |
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