|Mack, Christine Marie - AMYLIN PHARMACEUTICALS|
|Wilson, Jennifer - AMYLIN PHARMACEUTICALS|
|Athanacio, Jennifer - AMYLIN PHARMACEUTICALS|
|Reynolds, James - AMYLIN PHARMACEUTICALS|
|Guss, Stacy - AMYLIN PHARMACEUTICALS|
|Vu, Calvin - AMYLIN PHARMACEUTICALS|
|Roth, Jonathan - AMYLIN PHARMACEUTICALS|
|Parkes, David - AMYLIN PHARMACEUTICALS|
Submitted to: American Journal of Physiology - Regulatory Integrative & Comparative Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: September 7, 2007
Publication Date: September 12, 2007
Repository URL: http://ajpregu.physiology.org/cgi/reprint/293/5/R1855
Citation: Mack, C., Wilson, J., Athanacio, J., Reynolds, J., Laugero, K.D., Guss, S., Vu, C., Roth, J., Parkes, D. 2007. Pharmacological actions of the peptide hormone amylin in the long-term regulation of food intake, food preference, and body weight. American Journal of Physiology - Regulatory Integrative & Comparative Physiology. 293:R1855-R1863, 2007. Interpretive Summary: The pancreatic peptide hormone, amylin, is co-secreted with insulin in response to meals. It has well established glucoregulatory actions and its analogue is currently used with insulin for treating type 1 diabetes. However, this peptide hormone also inhibits food intake in rodent models and might serve as an antiobesity agent. This study assessed food preference, energy expenditure, and body composition in rats continuously administered amylin or vehicle. The results demonstrate pharmacological actions of amylin in long-term body weight regulation in part through its effects to curb food intake and, more interestingly, possibly by the peptide’s action on food preference and energy expenditure.
Technical Abstract: The ability of amylin to reduce acute food intake in rodents is well established. Longer-term administration in rats (up to 24 days) shows a concomitant reduction in body weight, suggesting energy intake plays a significant role in mediating amylin-induced weight loss. The current set of experiments further explores the long-term effects of amylin (4-11 wk) on food preference, energy expenditure, and body weight and composition. Furthermore, we describe the acute effect of amylin on locomotor activity and kaolin consumption to test for possible nonhomeostatic mechanisms that could affect food intake. Four-week subcutaneous amylin infusion of high-fat fed rats (3-300 microg.kg(-1).day(-1)) dose dependently reduced food intake and body weight gain (ED(50) for body weight gain = 16.5 microg.kg(-1).day(-1)). The effect of amylin on body weight gain was durable for up to 11 wks and was associated with a specific loss of fat mass and increased metabolic rate. The body weight of rats withdrawn from amylin (100 microg.kg(-1).day(-1)) after 4 wks of infusion returned to control levels 2 wks after treatment cessation, but did not rebound above control levels. When self-selecting calories from a low- or high-fat diet during 11 wks of infusion, amylin-treated rats (300 microg.kg(-1).day(-1)) consistently chose a larger percentage of calories from the low-fat diet vs. controls. Amylin acutely had no effect on locomotor activity or kaolin consumption at doses that decreased food intake. These results demonstrate pharmacological actions of amylin in long-term body weight regulation in part through appetitive-related mechanisms and possibly via changes in food preference and energy expenditure.