18-methoxycoronaridine and Body-Weight

Evidence suggests that the development of 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 Sprague-Dawley rats and administration of a selective antagonist of α3β4 nicotinic receptors, 18-methoxycoronaridine (18-MC), prevented this form of obesity. In the present study similar parameters were studied in male rats by using an identical experimental protocol. The effects of repeated administration of 18-MC on body weight gain, deposition of fat, consummatory behavior and biochemical markers of obesity in male rats were also assessed. In contrast to females, males consuming ad libitum quantities of sucrose solution (30%) in combination with normal chow did not become obese; they did not gain excessive weight nor show excessive fat deposition. Repeated administration of 18-MC (20mg/kg, i.p.) attenuated weight gain in both sucrose-consuming and control animals without altering food or fluid intake. The present results indicate that males and females are differentially responsive to high carbohydrate-diet obesity. Such gender disparities could be secondary to sex-specific alterations in cholinergic mechanisms of feeding and body weight regulation.

Topics: Analysis of Variance; Animals; Anti-Obesity Agents; Blood Glucose; Body Weight; Cholesterol; Disease Models, Animal; Drinking; Drug Administration Schedule; Eating; Female; Ibogaine; Male; Obesity; Rats; Rats, Sprague-Dawley; Sucrase; Weight Gain

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.

Topics: Analysis of Variance; Animals; Body Weight; Dietary Fats; Drug Administration Schedule; Eating; Energy Intake; Female; Ibogaine; Male; Nicotinic Antagonists; Obesity; Rats; Rats, Sprague-Dawley; Sex Characteristics; Weight Gain