Effect of metformin on nitric oxide synthase in genetically obese (ob/ob) mice

Genetically obese (ob/ob) mice were employed for the study of the effect of metformin on activity and expression of nitric oxide synthase (NOS) in vit ro and in vivo. For in vitro analysis, mouse liver extracts were used. For the in vivo study, (ob/ob) and their control litter mates (ob/c) mice were injected with specified amounts of metformin and the expression of NOS in t he adipose tissue and hypothalamus was measured by Western blotting. Result s show that metformin exhibited a biphasic effect on NOS activity in vitro. Expression of metformin was differentially altered in the hypothalamus and adipose tissues of the normal and ob/ob animals that were treated with met formin. Further, a significant decrease in food intake occurred in the (ob/ ob) mice that received metformin. This decrease in food intake was not acco mpanied by changes in serum glucose. At inhibitory concentrations, hypothal amic NOS expression changes differentially in normal and ob/ob mice. In nor mal mice, metformin stimulated NOS expression, while in ob/ob mice there wa s an inhibition. NOS expression increased in brown adipose tissue of metfor min treated control mice, while no such increase was observed in ob/ob mice . No effect of metformin was observed in white adipose tissue of control or obese mice. Thus, metformin may produce anorectic effects through modulati on of NOS. (C) 2001 Elsevier Science Inc. All rights reserved.