PLoS ONE (Jan 2013)

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 Beck Jørgensen,
  • Ka Ki Michelle Lee-Ng,
  • Hong Ping Zhang,
  • Liyun Wu,
  • Christopher Peter Marquis,
  • Lele Jiang,
  • Yasmin Husaini,
  • Shu Lin,
  • Herbert Herzog,
  • David A Brown,
  • Amanda Sainsbury,
  • Samuel N Breit

DOI
https://doi.org/10.1371/journal.pone.0055174
Journal volume & issue
Vol. 8, no. 2
p. e55174

Abstract

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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.