GDF15 mediates the effects of metformin on body weight and energy balance
Publication: Nature
Anthony P. Coll, Michael Chen, Stephen O’Rahilly et al
25 December 2019
Cambridge scientists have discovered that metformin causes the cells of the intestine to make large amounts of a hormone, called GDF15, and secrete it into the bloodstream.
The high blood levels of GDF15 are sensed by a highly specific area of the brain where they suppress hunger and reduce food intake. When GDF15 is blocked, metformin has no effect on body weight.
The work was undertaken in the MRC Metabolic Diseases Unit at the University of Cambridge with collaborators at NGM Biopharmaceuticals, the University of Glasgow and elsewhere.
Dr Tony Coll, a lead author, said “We usually think that drugs have to pass through the intestine to have their effects in the body. In this case, though, the cells of the intestine themselves respond to the drug to create a hormonal signal which does the work.”
Metformin has been used to treat Type 2 diabetes for over 60 years and is the world’s most commonly prescribed anti-diabetic drug. It can also prevent the onset of diabetes in those at risk, doing so by helping people to lose and keep off weight. However, how metformin reduces body weight has been a mystery.
Professor Stephen O’Rahilly said: “How metformin keeps body weight down has been a mystery. This work shows that all of this effect is down to GDF15 acting on a tiny number of cells in the brain.”
These findings are supported by an independent study from McMaster University published in Nature Metabolism and should stimulate research into the use of GDF15 itself as an anti-obesity agent.
