Important role of ventromedial hypothalamic carnitine palmitoyltransferase-1a in the control of food intake
| Autor: | Dolors Serra, Gary D. Lopaschuk, Wendy Keung, Su Gao, Fausto G. Hegardt |
|---|---|
| Přispěvatelé: | Universitat de Barcelona |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Male
endocrine system diseases Physiology Endocrinology Diabetes and Metabolism Rats Sprague-Dawley chemistry.chemical_compound Eating heterocyclic compounds Arc (protein) Hipotàlem Carnitina palmitoïl-transferasa 1 Fasting Dependovirus Malonyl Coenzyme A Hypothalamus medicine.drug medicine.medical_specialty endocrine system Blotting Western Genetic Vectors Fisiologia Biology Arcuate nucleus Physiology (medical) Internal medicine Orexigenic Brain Nucleus Carnitine Appetite Depressants medicine Animals Hypoglycemic Agents neoplasms Nutrició Injections Intraventricular Nutrition Carnitine O-Palmitoyltransferase Body Weight Arcuate Nucleus of Hypothalamus digestive system diseases Rats Enzyme Activation Endocrinology chemistry Ventromedial Hypothalamic Nucleus Anorectic Epoxy Compounds Carnitine palmitoyltransferase I Acyl Coenzyme A Etomoxir |
| Zdroj: | Dipòsit Digital de la UB Universidad de Barcelona Recercat. Dipósit de la Recerca de Catalunya instname |
| Popis: | 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 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. |
| Databáze: | OpenAIRE |
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