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...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24819600/?tool=EBI |
| _version_ | 1819100716105465856 |
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| author | Paula Mera Joan Francesc Mir Gemma Fabriàs Josefina Casas Ana S H Costa Maria Ida Malandrino José-Antonio Fernández-López Xavier Remesar Su Gao Shigeru Chohnan Maria Sol Rodríguez-Peña Harald Petry Guillermina Asins Fausto G Hegardt Laura Herrero Dolors Serra |
| author_facet | Paula Mera Joan Francesc Mir Gemma Fabriàs Josefina Casas Ana S H Costa Maria Ida Malandrino José-Antonio Fernández-López Xavier Remesar Su Gao Shigeru Chohnan Maria Sol Rodríguez-Peña Harald Petry Guillermina Asins Fausto G Hegardt Laura Herrero Dolors Serra |
| author_sort | Paula Mera |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-22T01:07:11Z |
| format | Article |
| id | doaj.art-0f52c75325a745c6b410747a6caa4d78 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T01:07:11Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-0f52c75325a745c6b410747a6caa4d782022-12-21T18:44:03ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0195e9719510.1371/journal.pone.0097195Long-term increased carnitine palmitoyltransferase 1A expression in ventromedial hypotalamus causes hyperphagia and alters the hypothalamic lipidomic profile.Paula MeraJoan Francesc MirGemma FabriàsJosefina CasasAna S H CostaMaria Ida MalandrinoJosé-Antonio Fernández-LópezXavier RemesarSu GaoShigeru ChohnanMaria Sol Rodríguez-PeñaHarald PetryGuillermina AsinsFausto G HegardtLaura HerreroDolors SerraLipid 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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24819600/?tool=EBI |
| spellingShingle | Paula Mera Joan Francesc Mir Gemma Fabriàs Josefina Casas Ana S H Costa Maria Ida Malandrino José-Antonio Fernández-López Xavier Remesar Su Gao Shigeru Chohnan Maria Sol Rodríguez-Peña Harald Petry Guillermina Asins Fausto G Hegardt Laura Herrero Dolors Serra Long-term increased carnitine palmitoyltransferase 1A expression in ventromedial hypotalamus causes hyperphagia and alters the hypothalamic lipidomic profile. PLoS ONE |
| 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 |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24819600/?tool=EBI |
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