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|Title:||Important role of ventromedial hypothalamic carnitine palmitoyltransferase-1a in the control of food intake|
Serra i Cucurull, Dolors
García Hegardt, Fausto
Lopaschuk, Gary D.
Carnitina palmitoïl-transferasa 1
Carnitine palmitoyltransferase I
|Publisher:||American Physiological Society|
|Abstract:||Carnitine 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 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, 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 altered in concert with fasting and refeeding states, supporting a physiological role of CPT-1a in mediating the control of feeding. Taking together, CPT-1a in the hypothalamic VMN appears to play an important role in the 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.|
|Note:||Versió postprint del document publicat a: http://dx.doi.org/10.1152/ajpendo.00168.2013|
|It is part of:||American Journal of Physiology-Endocrinology and Metabolism, 2013, vol. 305, num. 3, p. E336-E347|
|Appears in Collections:||Articles publicats en revistes (Bioquímica i Biomedicina Molecular)|
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