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Article: Important role of ventromedial hypothalamic carnitine palmitoyltransferase-1a in the control of food intake

TitleImportant role of ventromedial hypothalamic carnitine palmitoyltransferase-1a in the control of food intake
Authors
Issue Date2013
Citation
American Journal of Physiology - Endocrinology and Metabolism, 2013, v. 305 n. 3, p. E336-E347 How to Cite?
AbstractCarnitine palmitoyltransferase-1 (CPT-1) liver isoform, or CPT-1a, is implicated in CNS control of food intake. However, the exact brain nucleus site(s) in mediating this action of CPT-1a has not been identified. In this report, we assess the role of CPT-1a in hypothalamic ventromedial nucleus (VMN). We stereotaxically injected an adenoviral vector containing CPT-1a coding sequence into the VMN of rats to induce overexpression and activation of CPT-1a. The VMN-selective activation of CPT-1a induced an orexigenic effect, suggesting CPT-1a in the VMN is involved in the central control of feeding. Intracerebroventricular administration of etomoxir, a CPT-1 inhibitor, decreases food intake. Importantly, in the animals with VMN overexpression of a CPT-1a mutant that antagonizes the CPT-1 inhibition by etomoxir, the anorectic response to etomoxir was attenuated. This suggests that VMN is involved in mediating the anorectic effect of central inhibition of CPT-1a. In contrast, arcuate nucleus (Arc) overexpression of the mutant did not alter etomoxir-induced inhibition of food intake, suggesting that Arc CPT-1a does not play significant roles in this anorectic action. Furthermore, in the VMN, CPT-1a appears to act downstream of hypothalamic malonyl-CoA action of feeding. Finally, we show that in the VMN CPT-1 activity was altered in concert with fasting and refeeding states, supporting a physiological role of CPT-1a in mediating the control of feeding. All together, CPT-1a in the hypothalamic VMN appears to play an important role in central control of food intake. VMN-selective modulation of CPT-1a activity may therefore be a promising strategy in controlling food intake and maintaining normal body weight. © 2013 the American Physiological Society.
Persistent Identifierhttp://hdl.handle.net/10722/195873
ISSN
2015 Impact Factor: 3.825
2015 SCImago Journal Rankings: 2.465
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorGao, S-
dc.contributor.authorSerra, D-
dc.contributor.authorKeung, W-
dc.contributor.authorHegardt, FG-
dc.contributor.authorLopaschuk, GD-
dc.date.accessioned2014-03-19T01:46:12Z-
dc.date.available2014-03-19T01:46:12Z-
dc.date.issued2013-
dc.identifier.citationAmerican Journal of Physiology - Endocrinology and Metabolism, 2013, v. 305 n. 3, p. E336-E347-
dc.identifier.issn0193-1849-
dc.identifier.urihttp://hdl.handle.net/10722/195873-
dc.description.abstractCarnitine palmitoyltransferase-1 (CPT-1) liver isoform, or CPT-1a, is implicated in CNS control of food intake. However, the exact brain nucleus site(s) in mediating this action of CPT-1a has not been identified. In this report, we assess the role of CPT-1a in hypothalamic ventromedial nucleus (VMN). We stereotaxically injected an adenoviral vector containing CPT-1a coding sequence into the VMN of rats to induce overexpression and activation of CPT-1a. The VMN-selective activation of CPT-1a induced an orexigenic effect, suggesting CPT-1a in the VMN is involved in the central control of feeding. Intracerebroventricular administration of etomoxir, a CPT-1 inhibitor, decreases food intake. Importantly, in the animals with VMN overexpression of a CPT-1a mutant that antagonizes the CPT-1 inhibition by etomoxir, the anorectic response to etomoxir was attenuated. This suggests that VMN is involved in mediating the anorectic effect of central inhibition of CPT-1a. In contrast, arcuate nucleus (Arc) overexpression of the mutant did not alter etomoxir-induced inhibition of food intake, suggesting that Arc CPT-1a does not play significant roles in this anorectic action. Furthermore, in the VMN, CPT-1a appears to act downstream of hypothalamic malonyl-CoA action of feeding. Finally, we show that in the VMN CPT-1 activity was altered in concert with fasting and refeeding states, supporting a physiological role of CPT-1a in mediating the control of feeding. All together, CPT-1a in the hypothalamic VMN appears to play an important role in central control of food intake. VMN-selective modulation of CPT-1a activity may therefore be a promising strategy in controlling food intake and maintaining normal body weight. © 2013 the American Physiological Society.-
dc.languageeng-
dc.relation.ispartofAmerican Journal of Physiology - Endocrinology and Metabolism-
dc.titleImportant role of ventromedial hypothalamic carnitine palmitoyltransferase-1a in the control of food intake-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1152/ajpendo.00168.2013-
dc.identifier.pmid23736540-
dc.identifier.scopuseid_2-s2.0-84880983513-
dc.identifier.hkuros239599-
dc.identifier.volume305-
dc.identifier.issue3-
dc.identifier.spageE336-
dc.identifier.epageE347-
dc.identifier.isiWOS:000322701700004-

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