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PloS one 2013;8(2):e55174. doi: 10.1371/journal.pone.0055174. Epub 2013 Feb 28.

TGF-b Superfamily Cytokine MIC-1/GDF15 Is a Physiological Appetite and Body Weight Regulator.

Tsai, VW; Macia, L; Johnen, H; Kuffner, T; Manadhar, R; Jørgensen, SB; Lee-Ng, KK; Zhang, HP; Wu, L; Marquis, CP; Jiang, L; Husaini, Y; Lin, S; Herzog, H; Brown, DA; Sainsbury, A; Breit, SN

St Vincent's Centre for Applied Medical Research, St Vincent's Hospital and University of New South Wales, Sydney, New South Wales, Australia.

Abstract:
The TGF-b superfamily cytokine MIC-1/GDF15 circulates in all humans and when overproduced in cancer leads to anorexia/cachexia, by direct action on brain feeding centres. In these studies we have examined the role of physiologically relevant levels of MIC-1/GDF15 in the regulation of appetite, body weight and basal metabolic rate. MIC-1/GDF15 gene knockout mice (MIC-1) weighed more and had increased adiposity, which was associated with increased spontaneous food intake. Female MIC-1 mice exhibited some additional alterations in reduced basal energy expenditure and physical activity, possibly owing to the associated decrease in total lean mass. Further, infusion of human recombinant MIC-1/GDF15 sufficient to raise serum levels in MIC-1 mice to within the normal human range reduced body weight and food intake. Taken together, our findings suggest that MIC-1/GDF15 is involved in the physiological regulation of appetite and energy storage.

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