Journal
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
Volume 293, Issue 5, Pages R1855-R1863Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00297.2007
Keywords
body composition; meal size; locomotor activity; kaolin consumption; pramlintide
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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 mu g center dot kg (-1)center dot day(-1)) dose dependently reduced food intake and body weight gain (ED50 for body weight gain = 16.5 mu g center dot kg (-1)center dot 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 The body weight of rats withdrawn from amylin ( 100 mu g center dot kg(-1)day(-1)) after 4 wks of infusion returned to control levels 2 wks after treatment cessation, but did not rebound above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 mu g center dot kg(-1)center dot 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.
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