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Am J Physiol Endocrinol Metab (August 14, 2007). doi:10.1152/ajpendo.00395.2007
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Submitted on June 21, 2007
Accepted on August 8, 2007

Effects of Prior or Concurrent Food Restriction on Amylin-Induced Changes in Body Weight and Body Composition in High-Fat Fed Female Rats

Jonathan Roth1*, Heather Hughes1, Todd Coffey1, Holly Maier1, James L Trevaskis1, and Christen M Anderson1

1 Amylin Pharmaceuticals, Inc., San Diego, California, United States

* To whom correspondence should be addressed. E-mail: jonathan.roth{at}amylin.com.

Amylin infusion reduces food intake and slows body weight gain in rodents. In obese male rats, amylin (but not pair-feeding) caused a preferential reduction of fat mass with protein preservation despite equal body weight loss in amylin-treated (fed ad-libitum) and pair-fed rats. In the present study, the effect of prior or concurrent food restriction on the ability of amylin to cause weight loss was evaluated. Retired female breeder rats were maintained on a high-fat diet (40% fat) for 9 weeks. Prior to drug treatment, rats were either fed ad-libitum or food-restricted for 10 days to lose 5% of their starting body weight. They were then sub divided into treatment groups that received either vehicle or amylin (100 µg/kg·day via subcutaneous mini-pump) and placed under either a restricted or ad-libitum feeding schedule (for a total of 8 treatment arms). Amylin 1) significantly reduced body weight compared to vehicle under all treatment conditions, except in always restricted animals, 2) significantly decreased percent body fat in all groups, and 3) preserved lean mass in all groups. These results indicate that amylin's anorexigenic and fat-specific weight loss properties can be extended to a variety of nutritive states in female rats.




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J. D. Roth, H. Maier, S. Chen, and B. L. Roland
Implications of Amylin Receptor Agonism: Integrated Neurohormonal Mechanisms and Therapeutic Applications
Arch Neurol, March 1, 2009; 66(3): 306 - 310.
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