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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

Laboratory of Molecular and Cellular Medicine, Departments of Cellular and Physiological Sciences and Surgery, Life Sciences Institute, University of British Columbia, Vancouver, Canada

Submitted 6 April 2007 ; accepted in final form 14 April 2008

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 µg·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 µg·kg body wt^–1·day^–1) 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 µg·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 µg·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).

obesity; food intake; osmotic minipumps; body weight; hormones

This article has been cited by other articles:

				E. Karra, K. Chandarana, and R. L. Batterham The role of peptide YY in appetite regulation and obesity J. Physiol., January 1, 2009; 587(1): 19 - 25. [Abstract] [Full Text] [PDF]

				R. D. Reidelberger, A. C. Haver, P. K. Chelikani, and J. L. Buescher Effects of different intermittent peptide YY (3-36) dosing strategies on food intake, body weight, and adiposity in diet-induced obese rats Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2008; 295(2): R449 - R458. [Abstract] [Full Text] [PDF]