Acute increase in food intake after intraperitoneal injection of metformin in rats

We studied the effect of intraperitoneal injection of different doses of the antihyperglycemic agent metformin on food intake and plasma metabolites (glucose, free fatty acids, beta-hydroxybutyrate) in rats fed a high-fat (HF) or a high-carbohydrate (HC) diet. Unexpectedly, metformin, at a dose of 120 mg/kg b.wt. stimulated food intake in both HF- and HC-fed rats, without affecting blood glucose level. This result is in contrast with the hitherto performed studies that found an anorectic effect of metformin in rodents. It is postulated that the hyperphagic effect of metformin might be related to reduced energy availability to hepatic metabolic sensors controlling food intake, because metformin's known inhibitory effect on oxidative phosphorylation mainly affects the hepatoportal area, and blockade of oxidative phosphorylation in this area has been shown to stimulate feeding.