CALL FOR PAPERS Neural Integration of Peripheral Signals Implicated in the Control of Energy Homeostasis and Metabolism Leptin extends the anorectic effects of chronic PYY(3-36) administration in ad libitum-fed rats

Unniappan S, Kieffer TJ. Leptin extends the anorectic effects of chronic PYY(3-36) administration in ad libitum-fed rats. Am J Physiol Regul Integr Comp Physiol 295: R51–R58, 2008. First published April 16, 2008; doi:10.1152/ajpregu.00234.2007.—Acute administration of peptide YY(3-36) [PYY(3-36)] results in a reduction in food intake in several different vertebrates. However, long-term continuous administration of PYY(3-36) causes only a transient reduction in food intake, thus potentially limiting its therapeutic efficacy. We hypothesized that a fall in leptin levels associated with reduced food intake could contribute to the transient anorectic effects of continuous PYY(3-36) infusion and thus that leptin replacement might prolong the anorectic effects of PYY(3-36). Seven-day administration of 100 g kg body wt 1 day 1 PYY(3-36) using osmotic minipumps caused a significant reduction in food intake of ad libitum-fed rats, but only for the first 2 days postimplantation. Circulating levels of leptin were reduced 1 day following continuous infusion of PYY(3-36), and combined leptin infusion at a dose of leptin that had no anorectic effects on its own (100 g kg body wt 1 day ) prolonged the anorectic actions of PYY(3-36) in ad libitum-fed rats for up to 6 days postimplantation and yielded reduced weight gain compared with either peptide alone. The inhibitory effects of 100 g kg body wt 1 day 1 PYY(3-36) on food intake were absent in rats refed after a 24-h fast and substantially reduced at a dose of 1,000 g kg body wt 1 day 1 PYY(3-36). Leptin replacement was unable to recover the anorectic effects of PYY(3-36) in fasted rats. Our results suggest that an acute fall in leptin levels is not solely responsible for limiting duration of action of chronic PYY(3-36) infusion, yet chronic coadministration of a subanorectic dose of leptin can extend the anorectic effects of PYY(3-36).