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Am J Physiol Endocrinol Metab 297: E1269-E1275, 2009. First published September 29, 2009; doi:10.1152/ajpendo.00337.2009
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Regulation of food intake and body weight by recombinant proghrelin

Weizhen Zhang,1,2 Arundhati Majumder,1 Xiaobin Wu,1 and Michael W. Mulholland1

1Department of Surgery, University of Michigan, Ann Arbor, Michigan; and 2Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China

Submitted 22 May 2009 ; accepted in final form 19 September 2009

Ghrelin is a 28-amino-acid hormone derived from the endoproteolytic processing of its prehormone proghrelin. Although ghrelin has been reported to regulate food intake and body weight, it is still unknown whether proghrelin exercises any biological function. Here we show that recombinant proghrelin alters food intake and energy metabolism in mice. After intraperitoneal administration of recombinant proghrelin (100 nmol/kg body wt), cumulative food intake was significantly increased at days 1, 2, and 3 (6 ± 0.3, 13 ± 0.5, and 20 ± 0.8 g vs. 5 ± 0.2, 10 ± 0.2, and 16 ± 0.3 g of the control mice receiving normal saline, respectively, n = 6, P < 0.05). Twelve-hour cumulative food intake in the light photo period in mice treated with proghrelin increased significantly relative to the control (2.1 ± 0.04 vs. 1.3 ± 0.2 g, n = 6, P < 0.05). No change in 12-h cumulative food intake in the dark photo period was observed between mice treated with proghrelin and vehicle (4.2 ± 0.6 vs. 4.3 ± 0.6 g, n = 6, P > 0.05). This is associated with a decrease in body weight (0.42 ± 0.04 g) for mice treated with proghrelin, whereas control animals gained body weight (0.31 ± 0.04 g). Mice treated with proghrelin demonstrate a significant decrease in respiratory quotient, indicating an increase in fat consumption. Recombinant proghrelin is functionally active with effects on food intake and energy metabolism.

ghrelin; proghrelin; food intake; body weight; respiratory quotient



Address for reprint requests and other correspondence: W. Zhang, 1520B, MSRB I, 1150 W. Medical Center Dr., Ann Arbor, MI 48109-0666 (e-mail: weizhenz{at}umich.edu).







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