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Submitted on March 28, 2006
Accepted on August 15, 2006
-Cell Hormone Amylin in Diet Induced Obese Rats: Effects on Food Intake, Body Weight, Composition, Energy Expenditure and Gene Expression
Amylin Pharmaceuticals, Inc. San Diego, California, 92121
* To whom correspondence should be addressed. E-mail: jonathan.roth{at}amylin.com.
Effects of amylin and pair-feeding (PF) on body weight and metabolic parameters were characterized in diet-induced obesity (DIO) prone rats. Peripherally administered rat amylin (300 µg/kg/day, 22d) reduced food intake and slowed weight gain: 
10% (P < 0.05), similar to PF. Fat loss was 3-fold greater in amylin-treated rats vs. PF (P < 0.05). While PF decreased lean tissue (P < 0.05 vs. vehicle controls; VEH), amylin did not. During Wk1, amylin and PF reduced 24 h respiratory quotient (RQ 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 ± 0.1kcal/h/kg) and maintained by amylin (5.86 ± 0.1kcal/h/kg) relative to VEH (5.77 ± 0.0kcal/h/kg). By Wk3, RQ no longer differed; however, EE increased with amylin treatment (5.74 ± 0.09kcal/h/kg; P < 0.05) relative to VEH (5.49 ± 0.06) and PF (5.38 ± 0.07kcal/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 pro-opiomelanocortin mRNA levels (P < 0.05 vs. vehicle controls). 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.
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