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- Publisher Website: 10.1152/ajpregu.00092.2011
- Scopus: eid_2-s2.0-79959332640
- PMID: 21508288
- WOS: WOS:000292319800020
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Article: Malonyl-CoA mediates leptin hypothalamic control of feeding independent of inhibition of CPT-1a
Title | Malonyl-CoA mediates leptin hypothalamic control of feeding independent of inhibition of CPT-1a |
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Authors | |
Keywords | Carnitine palmitoyltransferase Food intake Hypothalamus |
Issue Date | 2011 |
Citation | American Journal of Physiology - Regulatory Integrative and Comparative Physiology, 2011, v. 301 n. 1, p. R209-R217 How to Cite? |
Abstract | Hypothalamic fatty acid metabolism is involved in central nervous system controls of feeding and energy balance. Malonyl-CoA, an intermediate of fatty acid biosynthesis, is emerging as a significant player in these processes. Notably, hypothalamic malonyl-CoA has been implicated in leptin's feeding effect. Leptin treatment increases malonyl- CoA level in the hypothalamic arcuate nucleus (Arc), and this increase is required for leptin-induced decrease in food intake. However, the intracellular downstream mediators of malonyl-CoA's feeding effect have not been identified. A primary biochemical action of malonyl- CoA is the inhibition of the acyltransferase activity of carnitine palmitoyltransferase-1 (CPT-1). In the hypothalamus, the predominant isoform of CPT-1 that possesses the acyltransferase activity is CPT-1 liver type (CPT-1a). To address the role of CPT-1a in malonyl- CoA's anorectic action, we used a recombinant adenovirus expressing a mutant CPT-1a that is insensitive to malonyl-CoA inhibition. We show that Arc overexpression of the mutant CPT-1a blocked the malonyl-CoA-mediated inhibition of CPT-1 activity. However, the overexpression of this mutant did not affect the anorectic actions of leptin or central cerulenin for which an increase in Arc malonyl-CoA level is also required. Thus, CPT-1a does not appear to be involved inthe malonyl-CoA's anorectic actions induced by leptin. Furthermore, long-chain fatty acyl-CoAs, substrates of CPT-1a, dissociate from malonyl-CoA's actions in the Arc under different feeding states. Together, our results suggest that Arc intracellular mechanisms of malonyl-CoA's anorectic actions induced by leptin are independent of CPT-1a. The data suggest that target(s), rather than CPT-1a, mediates malonyl-CoA action on feeding. © 2011 the American Physiological Society. |
Persistent Identifier | http://hdl.handle.net/10722/195861 |
ISSN | 2023 Impact Factor: 2.2 2023 SCImago Journal Rankings: 0.904 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Gao, S | - |
dc.contributor.author | Keung, W | - |
dc.contributor.author | Serra, D | - |
dc.contributor.author | Wang, W | - |
dc.contributor.author | Carrasco, P | - |
dc.contributor.author | Casals, N | - |
dc.contributor.author | Hegardt, FG | - |
dc.contributor.author | Moran, TH | - |
dc.contributor.author | Lopaschuk, GD | - |
dc.date.accessioned | 2014-03-19T01:46:11Z | - |
dc.date.available | 2014-03-19T01:46:11Z | - |
dc.date.issued | 2011 | - |
dc.identifier.citation | American Journal of Physiology - Regulatory Integrative and Comparative Physiology, 2011, v. 301 n. 1, p. R209-R217 | - |
dc.identifier.issn | 0363-6119 | - |
dc.identifier.uri | http://hdl.handle.net/10722/195861 | - |
dc.description.abstract | Hypothalamic fatty acid metabolism is involved in central nervous system controls of feeding and energy balance. Malonyl-CoA, an intermediate of fatty acid biosynthesis, is emerging as a significant player in these processes. Notably, hypothalamic malonyl-CoA has been implicated in leptin's feeding effect. Leptin treatment increases malonyl- CoA level in the hypothalamic arcuate nucleus (Arc), and this increase is required for leptin-induced decrease in food intake. However, the intracellular downstream mediators of malonyl-CoA's feeding effect have not been identified. A primary biochemical action of malonyl- CoA is the inhibition of the acyltransferase activity of carnitine palmitoyltransferase-1 (CPT-1). In the hypothalamus, the predominant isoform of CPT-1 that possesses the acyltransferase activity is CPT-1 liver type (CPT-1a). To address the role of CPT-1a in malonyl- CoA's anorectic action, we used a recombinant adenovirus expressing a mutant CPT-1a that is insensitive to malonyl-CoA inhibition. We show that Arc overexpression of the mutant CPT-1a blocked the malonyl-CoA-mediated inhibition of CPT-1 activity. However, the overexpression of this mutant did not affect the anorectic actions of leptin or central cerulenin for which an increase in Arc malonyl-CoA level is also required. Thus, CPT-1a does not appear to be involved inthe malonyl-CoA's anorectic actions induced by leptin. Furthermore, long-chain fatty acyl-CoAs, substrates of CPT-1a, dissociate from malonyl-CoA's actions in the Arc under different feeding states. Together, our results suggest that Arc intracellular mechanisms of malonyl-CoA's anorectic actions induced by leptin are independent of CPT-1a. The data suggest that target(s), rather than CPT-1a, mediates malonyl-CoA action on feeding. © 2011 the American Physiological Society. | - |
dc.language | eng | - |
dc.relation.ispartof | American Journal of Physiology - Regulatory Integrative and Comparative Physiology | - |
dc.subject | Carnitine palmitoyltransferase | - |
dc.subject | Food intake | - |
dc.subject | Hypothalamus | - |
dc.title | Malonyl-CoA mediates leptin hypothalamic control of feeding independent of inhibition of CPT-1a | - |
dc.type | Article | - |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.1152/ajpregu.00092.2011 | - |
dc.identifier.pmid | 21508288 | - |
dc.identifier.scopus | eid_2-s2.0-79959332640 | - |
dc.identifier.hkuros | 239594 | - |
dc.identifier.volume | 301 | - |
dc.identifier.issue | 1 | - |
dc.identifier.spage | R209 | - |
dc.identifier.epage | R217 | - |
dc.identifier.isi | WOS:000292319800020 | - |
dc.identifier.issnl | 0363-6119 | - |