The efficacy of a dopamine D2 agonist in treating obesity and obesity-related conditions in rodent models.

摘要

The primary goal of this study was to determine the effectiveness of the dopamine D2 agonist, bromocriptine, in reversing the central (reward deficiency), and the peripheral (body composition and metabolic) defects of obesity. To test its effectiveness, and elucidate its mechanism of action (MOA), we performed a randomized controlled experiment examining two genetic models and one environmental model of obesity: (fa/fa) Zucker rats and ob/ob mice; and a rat model of diet-induced obesity (DIO).; Bromocriptine significantly improved the central (reward deficiency) defects in genetically obese and diet-induced obese (DIO) rodents. Food intake was significantly reduced compared to pre-treatment measurements each week of the 4-week treatment phase in Zucker and DIO rats. Among ob mice, there was a trend toward reduced food intake during weeks 1 and 2. Locomotor activity was significantly increased during the 12-hr (dark) phase and 22-hr phase in bromocriptine-treated Zucker and DIO rats compared to fatty controls.; In the periphery, bromocriptine significantly reduced epididymal fat pads in DIO rats and ob mice compared to controls. Hepatic lipids were significantly reduced in all models of obesity compared with fatty controls. Manganese superoxide dismutase (MnSOD), an antioxidant enzyme, and blood glucose, were significantly increased in treated Zucker rats compared with fatty controls.; Compared with controls, we observed significant increases in dopamine D2 receptor binding in bromocriptine-treated Zucker rats and ob/ob mice in both striatal and lateral hypothalamic regions. Among genetically obese rodents, increases in D2 receptor binding correlated inversely with food intake, body fat, and hepatic fat and positively with locomotor activity and MnSOD. We found significant increases in dopamine transporter (DAT) in the nucleus accumbens (NA) shell in DIO rats, but no differences in DRD2 binding, indicating a likely different MOA by which bromocriptine exerts its antiobesity effects in genetically-obese and diet-induced obese rodents.