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Accepted Preprint first posted online on 9 May 2008

Journal of Endocrinology 2008;198:157.

Journal of Endocrinology (2008) In press  DOI: 10.1677/JOE-07-0428
© 2008 Society for Endocrinology

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RESEARCH-ARTICLE

Intracerebroventricular injection of citrate inhibits hypothalamic AMPK and modulates feeding behavior and peripheral insulin signaling

Graziela Stoppa, Maristela Cesquini, Erika Roman, Patricia Prada, Adriana Torsoni, Talita Romanatto, Mario Saad, Licio Velloso and Marcio Torsoni

G Stoppa, Bioquímica, UNICAMP, Campinas, Brazil
M Cesquini, Bioquímica, UNICAMP, Campinas, Brazil
E Roman, Bioquímica, UNICAMP, Campinas, Brazil
P Prada, Clinica Médica, UNICAMP, Campinas, Brazil
A Torsoni, Area da Saude, Universidade Braz Cubas, Mogi das Cruzes, Brazil
T Romanatto, Clinica Médica, UNICAMP, Campinas, Brazil
M Saad, Clinica Médica, UNICAMP, Campinas, Brazil
L Velloso, Campinas, Brazil
M Torsoni, Área da Saude, Universidade Braz Cubas, Mogi das Cruzes, 08773-380, Brazil

Correspondence: Marcio Torsoni, Email: torsoni{at}yahoo.com

Abstract

We hypothesized that citrate might modulate the 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 phosphorylation of hypothalamic AMPK/ACC, increased anorexigenic neuropeptide (POMC and CRH) expression, and reduced food intake. With euglycemic hyperinsulinemic clamp, the rate of glucose infusion 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), as was glucose uptake in skeletal muscle and the epididymal fat pad. Concordantly, IR, IRS1, IRS2, and AKT phosphorylation in adipose tissue and skeletal muscle were improved by citrate ICV treatment. Moreover, the treatment with citrate for seven days promoted body weight loss and decreased the adipose tissue. Our results suggest that citrate as well as glucose may serve to hypothalamus as cell signals of energy and nutrient availability.







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