title: Sex differences in high fat-induced obesity in rats: Effects of 18-methoxycoronaridine.
abstract: 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.
authors.affiliation: Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, NY, United States. tarasco@mail.amc.edu
authors.forename: Olga D
authors.initials: OD
authors.lastname: Taraschenko
authors.forename: Isabelle M
authors.initials: IM
authors.lastname: Maisonneuve
authors.forename: Stanley D
authors.initials: SD
authors.lastname: Glick
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004041:Dietary Fats / Q000009:adverse effects*; D004334:Drug Administration Schedule; D004435:Eating / Q000187:drug effects; D002149:Energy Intake / Q000187:drug effects; D005260:Female; D007050:Ibogaine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008297:Male; D018733:Nicotinic Antagonists / Q000008:administration & dosage*; D009765:Obesity / Q000188:drug therapy* / Q000209:etiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D015430:Weight Gain / Q000187:drug effects
chemical_list: D004041:Dietary Fats; D018733:Nicotinic Antagonists; D007050:Ibogaine; C103345:18-methoxycoronaridine