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Article: Malonyl-CoA mediates leptin hypothalamic control of feeding independent of inhibition of CPT-1a

TitleMalonyl-CoA mediates leptin hypothalamic control of feeding independent of inhibition of CPT-1a
Authors
Issue Date2011
Citation
American Journal of Physiology - Regulatory Integrative and Comparative Physiology, 2011, v. 301 n. 1, p. R209-R217 How to Cite?
AbstractHypothalamic 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 Identifierhttp://hdl.handle.net/10722/195861
ISSN
2015 Impact Factor: 3.168
2015 SCImago Journal Rankings: 1.663
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorGao, S-
dc.contributor.authorKeung, W-
dc.contributor.authorSerra, D-
dc.contributor.authorWang, W-
dc.contributor.authorCarrasco, P-
dc.contributor.authorCasals, N-
dc.contributor.authorHegardt, FG-
dc.contributor.authorMoran, TH-
dc.contributor.authorLopaschuk, GD-
dc.date.accessioned2014-03-19T01:46:11Z-
dc.date.available2014-03-19T01:46:11Z-
dc.date.issued2011-
dc.identifier.citationAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology, 2011, v. 301 n. 1, p. R209-R217-
dc.identifier.issn0363-6119-
dc.identifier.urihttp://hdl.handle.net/10722/195861-
dc.description.abstractHypothalamic 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.languageeng-
dc.relation.ispartofAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology-
dc.titleMalonyl-CoA mediates leptin hypothalamic control of feeding independent of inhibition of CPT-1a-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1152/ajpregu.00092.2011-
dc.identifier.pmid21508288-
dc.identifier.scopuseid_2-s2.0-79959332640-
dc.identifier.hkuros239594-
dc.identifier.volume301-
dc.identifier.issue1-
dc.identifier.spageR209-
dc.identifier.epageR217-
dc.identifier.isiWOS:000292319800020-

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