ANORECTIC EFFECT OF METFORMIN IN OBESE ZUCKER RATS - LACK OF EVIDENCEFOR THE INVOLVEMENT OF NEUROPEPTIDE-Y

The hypothalamic neuropeptide Y content and preproneuropeptide Y mRNA expression were studied in metformin-treated (300 mg/kg orally for 12 days), in pair-fed and in ad libitum-fed obese Zucker rats in order to elucidate possible mechanisms involved in the anorectic and body weig ht reducing effect of chronic metformin treatment in genetically obese Zucker rats. In addition the acute influence of metformin on food int ake was studied by comparing its effects after oral and parenteral adm inistration. The concentration of neuropeptide Y in the hypothalamic p araventricular nucleus was significantly higher in the metformin-treat ed and pair-fed rats when compared to the control animals. The express ion of preproneuropeptide Y mRNA in the arcuate nucleus was similar in all three treatment groups. Both chronic metformin treatment and pair -feeding markedly lowered hyperinsulinaemia in these animals. A single subcutaneous dose of metformin (300 mg/kg) reduced food intake only i n obese animals, while the same dose of metformin given orally did not affect food intake in either lean or obese animals. It is concluded t hat the treatment with metformin and pair-feeding, which results in co mparable reductions in food intake, body weight gain and hyperinsulina emia, similarly increase neuropeptide Y concentrations in the paravent ricular nucleus while not affecting preproneuropeptide Y mRNA expressi on in the arcuate nucleus. The increase in hypothalamic neuropeptide Y content may be secondary to the reduction in hyperinsulinaemia during metformin treatment and pair-feeding. Thus, the anorectic effect of c hronic metformin treatment cannot be explained by changes in content o r expression of hypothalamic neuropeptide Y.