TGF-b superfamily cytokine MIC-1/GDF15 is a physiological appetite and body weight regulator

Vicky Wang-Wei Tsai, Laurence Macia, Heiko Johnen, Tamara Kuffner, Rakesh Manadhar, Sebastian B Jorgensen, Ka Ki [Michelle] Lee-Ng, Hong Ping Ping Zhang, Liyun Wu, Christopher P Marquis, Lele Jiang, Yasmin Husaini, Shu Lin, Herbert Herzog, David A Brown, Amanda Sainsbury, Samuel N Breit

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    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.
    Original languageEnglish
    Article numbere55174
    Number of pages10
    JournalPLoS ONE
    Volume8
    Issue number2
    DOIs
    Publication statusPublished - 2013

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