HOME HELP CONTACT US SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: JOE-07-0428v1 198/1/157    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Stoppa, G. R Articles by Torsoni, M. A PubMed PubMed Citation Articles by Stoppa, G. R Articles by Torsoni, M. A

Departamento de Bioquímica, IB, Universidade Estadual de Campinas, Campinas, SP, Brazil¹ Departamento de Clinica Médica, Universidade Estadual de Campinas, CEP13.083-970 Campinas, SP, Brazil² Universidade Braz Cubas, Área da Saúde-Campus I, Av. Francisco Rodrigues Filho, 1233, Mogilar, Mogi das Cruzes CEP 08773-380, SP, Brazil

(Correspondence should be addressed to M A Torsoni; Email: torsoni{at}yahoo.com)

We hypothesized that citrate might modulate the AMP-activated protein kinase/acetyl-CoA carboxylase (AMPK)/(ACC) pathway and participate in neuronal feeding control and glucose homeostasis. To address this issue, we injected citrate into the lateral ventricle of rats. Intracerebroventricular (ICV) injection of citrate diminished the phosphorylation of hypothalamic AMPK/ACC, increased the expression of anorexigenic neuropeptide (pro-opiomelanocortin and corticotropin-releasing hormone), elevated the level of malonyl-CoA in the hypothalamus, and reduced food intake. No change was observed in the concentration of blood insulin after the injection of citrate. With a euglycemic–hyperinsulinemic clamp, the glucose infusion rate was higher in the citrate group than in the control group (28.6±0.8 vs 19.3±0.2 mU/kg body weight/min respectively), and so was glucose uptake in skeletal muscle and the epididymal fat pad. Concordantly, insulin receptor (IR), IR substrate type 1 (IRS1), IRS2, and protein kinase B (AKT) phosphorylation in adipose tissue and skeletal muscle was improved by citrate ICV treatment. Moreover, the treatment with citrate for 7 days promoted body weight loss and decreased the adipose tissue. Our results suggest that citrate and glucose may serve as signals of energy and nutrient availability to hypothalamic cells.