Work led by Stephen O’Rahilly, David Savage and Tony Coll from the Institute of Metabolic Science and MRC Metabolic Diseases Unit published online in Cell Metabolism brings new insights into how states of caloric overload are signalled to the brain.
Leptin is a well-known signal which informs the brain of the state of energy stores. However, with progressive obesity the brain stops responding to leptin. This new research identifies the TGF-beta like protein GDF15 as a hormone, the circulating levels of which are increased in the pathologically over-nourished state. Acting via specific receptors in the hind-brain, GDF15 provides an aversive signal which serves to suppress food intake. GDF15 is being actively pursued as a therapy for obesity and antagonists of this hormone are being trialled in cachexia. The work described in this paper, which was undertaken with multiple national and international collaborators including scientists at Pfizer Inc., provides new information highly relevant to these important translational initiatives.