Effect of competitive antagonism of NO synthetase on weight and food intake in obese and diabetic mice.

Recent studies have suggested a role for nitric oxide (NO) in the regulation of food intake. The present studies were undertaken to examine the effects of the administration of a nitric oxide synthetase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), on food intake and weight loss. Two genetically obese mice, the ob/ob and db/db strains, and their lean heterozygote littermate controls, ob/c and db/c, served as subjects. In the first experiment, we demonstrated that L-NAME (100 micrograms/kg) given twice over a feeding period of 7 h/day produced a small but significant weight loss in ob/ob mice but not in their lean-genotype controls (P < 0.05). In the second experiment, a higher dose of L-NAME (100 mg/kg), given twice daily, produced a marked effect on body weight, with the ob/ob mice losing approximately 10% of their body weight in 9 days. The ob/c mice showed a lesser decrease in body weight. Food intake was decreased on all 9 days in the ob/ob mice (P < 0.01). A small decrease in body weight and food intake was seen in db/db and db/c mice receiving L-NAME. These studies provide further evidence for a role of nitric oxide in the modulation of food intake and weight gain.