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Endocrinology, doi:10.1210/en.2006-0393
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Endocrinology Vol. 147, No. 12 5855-5864
Copyright © 2006 by The Endocrine Society

Antiobesity Effects of the ß-Cell Hormone Amylin in Diet-Induced Obese Rats: Effects on Food Intake, Body Weight, Composition, Energy Expenditure, and Gene Expression

Jonathan D. Roth, Heather Hughes, Eric Kendall, Alain D. Baron and Christen M. Anderson

Amylin Pharmaceuticals, Inc., San Diego, California 92121

Address all correspondence and requests for reprints to: Jonathan D. Roth, Ph.D., Amylin Pharmaceuticals, Inc., San Diego, California 92121. 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-prone rats. Peripherally administered rat amylin (300 µg/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 to VEH (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.




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