Sex differences in high fat-induced obesity in rats: Effects of 18-methoxycoronaridine.

Evidence suggests that the development of diet-induced obesity in males and females might be mediated by distinct mechanisms, warranting different treatment approaches. In previous studies from this laboratory, a high sucrose diet induced excessive weight gain in female but not in male Sprague-Dawley rats, while weight gain in both sexes was similarly attenuated by the administration of a selective antagonist of α3β4 nicotinic receptors, 18-methoxycoronaridine (18-MC). In the present study, assessment of high-fat induced weight gain, consummatory behavior and biochemical markers of obesity was conducted in male and female Sprague-Dawley rats and the effects of 18-MC treatment were compared in the two sexes. Male rats consuming a high-fat (HF) diet developed excessive weight gain and fat deposition compared to same same-sex controls fed with a low-fat (LF) diet. The development of obesity in these rats was attenuated by repeated administration of 18-MC (20mg/kg, i.p.), which significantly reduced their food intake without altering water intake. In contrast, female rats consuming a HF diet did not become obese and did not respond to 18-MC treatment. These results show that males and females are differentially responsive to HF-induced obesity; the 18-MC data suggest that α3β4 nicotinic receptors may participate in maintaining obesity, possibly becoming a new and important target for anti-obesity agents.