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This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 297/2/E545    most recent 00255.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Bechtold, D. A. Articles by Luckman, S. M. PubMed PubMed Citation Articles by Bechtold, D. A. Articles by Luckman, S. M.

Appetite-modifying actions of pro-neuromedin U-derived peptides

Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom

Submitted 23 April 2009 ; accepted in final form 11 June 2009

Neuromedin U (NMU) is known to have potent actions on appetite and energy expenditure. Deletion of the NMU gene in mice leads to an obese phenotype, characterized by hyperphagia and decreased energy expenditure. Conversely, transgenic mice that overexpress proNMU exhibit reduced body weight and fat storage. Here, we show that central administration of NMU or the related peptide neuromedin S (NMS) dose-dependently decreases food intake, increases metabolic rate, and leads to significant weight loss in mice. The effects of NMU and NMS on both feeding and metabolism are almost completely lost in mice lacking the putative CNS receptor for NMU and NMS, NMUr2. However, NMUr2 knockout mice do not exhibit overt differences in body weight or energy expenditure compared with wild-type mice, suggesting that the dramatic phenotype of the NMU gene knockout mouse is not due simply to the loss of NMU/NMUr2 signaling. Putative proteolytic cleavage sites indicate that an additional peptide is produced from the NMU precursor protein, which is extremely well conserved between human, mouse, and rat. Here, we demonstrate that this peptide, proNMU_104-136, has a pronounced effect on energy balance in mice. Specifically, central administration of proNMU_104-136 causes a significant but transient (4 h) increase in feeding, yet both food intake and body weight are decreased over the following 24 h. proNMU_104-136 administration also significantly increased metabolic rate. These results suggest that proNMU_104-136 is a novel modulator of energy balance and may contribute to the phenotype exhibited by NMU knockout mice.

metabolism; neuromedin S; neuromedin U receptor 2; obesity; energy expenditure