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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / growth & development
  • Animals
  • Appetite / genetics*
  • Appetite / physiology
  • Body Weight / genetics*
  • Body Weight / physiology
  • Eating
  • Energy Metabolism / genetics
  • Female
  • Genotype
  • Growth Differentiation Factor 15 / genetics*
  • Growth Differentiation Factor 15 / metabolism
  • Humans
  • Male
  • Mice
  • Mice, Knockout
  • Organ Size
  • Sex Factors
  • Signal Transduction
  • Weight Gain / genetics

Substances

  • Growth Differentiation Factor 15

Grants and funding

This work was supported by grants from the National Health and Medical Research Council of Australia (NHMRC). AS, DAB and HH are all recipients of NHMRC Career Development Awards or Fellowships. The funders had no role in study design, date collection and analysis, decision to publish, or preparation of the manuscript.