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APPETITE, OBESITY, DIGESTION, AND METABOLISM

PYY(3–36) reduces food intake and body weight and improves insulin sensitivity in rodent models of diet-induced obesity

Rheoscience, Rødovre, Denmark

Submitted 12 October 2005 ; accepted in final form 5 March 2006

The gut hormone peptide YY (PYY) was recently proposed to comprise an endogenous satiety factor. We have studied acute anorectic functions of PYY(3–36) in mice and rats, as well as metabolic effects of chronic PYY(3–36) administration to diet-induced obese (DIO) mice and rats. A single intraperitoneal injection of PYY(3–36) inhibited food intake in mice, but not in rats. We next investigated the effects of increasing doses (100, 300, and 1,000 µg·kg^–1·day^–1) of PYY(3–36) administered subcutaneously via osmotic minipumps on food intake and body weight in DIO C57BL/6J mice. Whereas only the highest dose (1,000 µg·kg^–1·day^–1) of PYY(3–36) significantly reduced food intake over the first 3 days, body weight gain was dose dependently reduced, and on day 28 the group treated with 1,000 µg·kg^–1·day^–1 PYY(3–36) weighed 10% less than the vehicle-treated group. Mesenteric, epididymal, retroperitoneal, and inguinal fat pad weight was dose dependently reduced. Subcutaneous administration of PYY(3–36) (250 and 1,000 µg·kg^–1·day^–1) for 28 days reduced body weight and improved glycemic control in glucose-intolerant DIO rats. Neither 250 nor 1,000 µg/kg PYY(3–36) elicited a conditioned taste aversion in male rats.

diet-induced obese rat; peptide YY; taste aversion; indirect calorimetry; locomotor activity

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