Antiobesity effects of the β-cell hormone amylin in diet-induced obese rats:: Effects on food intake, body weight, composition, energy expenditure, and gene expression

Effects of amylin and pair feeding (PF) on body weight and metabolic parameters were characterized in diet-induced obesity-prone rats. Peripherally administered rat amylin (300 mu g/kg(.)d, 22d) reduced food intake and slowed weight gain: approximately 10% (P < 0.05), similar to PF. Fat loss was 3-fold greater in amylin-treated rats vs. PF (P < 0.05). Whereas PF decreased lean tissue (P < 0.05 vs. vehicle controls; VEH), amylin did not. During wk 1, amylin and PF reduced 24-h respiratory quotient (mean +/- SE, 0.82 +/- 0.0, 0.81 +/- 0.0, respectively; P < 0.05) similar to VEH (0.84 +/- 0.01). Energy expenditure (EE mean +/- SE) tended to be reduced by PF (5.67 +/- 0.1 kcal/h(.)kg) and maintained by amylin (5.86 +/- 0.1 kcal/h(.)kg) relative to VEH (5.77 +/- 0.0 kcal/h(.)kg). By wk 3, respiratory quotient no longer differed; however, EE increased with amylin treatment (5.74 +/- 0.09 kcal/(.)kg; P <= 0.05) relative toVEH (5.49 +/- 0.06) and PF (5.38 +/- 0.07 kcal/h(.)kg). Differences in EE, attributed to differences in lean mass, argued against specific amylin-induced thermogenesis. Weight loss in amylin and pair-fed rats was accompanied by similar increases arcuate neuropeptide Y mRNA (P < 0.05). Amylin treatment, but not PF, increased proopiomelanocortin mRNA levels (P < 0.05 vs. VEH). In a rodent model of obesity, amylin reduced body weight and body fat, with relative preservation of lean tissue, through anorexigenic and specific metabolic effects.