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A Role for Galanin-Like Peptide in the Integration of Feeding, Body Weight Regulation, and Reproduction in the Mouse

Departments of Physiology and Biophysics (S.M.K., G.S.F., S.M.S., R.A.S.), Obstetrics and Gynecology (D.K.C., R.A.S.) and Zoology (R.A.S.), University of Washington, Seattle, Washington 98195-7290; and Amgen, Inc. (J.W.B.), Thousand Oaks, California 91320

Address all correspondence and requests for reprints to: Dr. Robert A. Steiner, Department of Physiology and Biophysics, University of Washington, Box 357290, Seattle, Washington 98195-7290. E-mail: steiner{at}u.washington.edu.

Galanin-like peptide (GALP) shares sequence homology with galanin and binds to galanin receptors in vitro. GALP neurons in the arcuate nucleus coexpress leptin receptors, and GALP mRNA expression is up-regulated by leptin. Based on these observations, we postulated that GALP plays a role in mediating leptin’s inhibitory effects on food intake (FI) and body weight (BW), as well as its stimulatory effect on the reproductive axis. To test these hypotheses, we performed several studies in which mice received intracerebroventricular injections of either GALP or vehicle. Acute GALP treatment elicited a dose-dependent suppression of FI and BW. Long-term treatment with GALP caused only transient reductions in FI and BW, demonstrating that the mice became refractory to continued exposure to GALP. GALP inhibited FI as early as 1 h post injection. Central injection of GALP suppressed locomotor activity and elicited the formation of a conditioned taste aversion. In male mice, serum levels of LH and testosterone were increased by GALP administration. Although we cannot rule out possible nonspecific effects of GALP on FI, the present observations are consistent with the argument that GALP is a downstream effector of leptin’s actions within the central nervous system.

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