Scientists working on weight-loss therapies have been investigating receptors on cell surfaces called G protein-coupled receptors.
One of these receptors, melanocortin 4 receptor, is expressed in the brain and is known to be involved in weight regulation. When activated in animal tests, it has been found to suppress appetite and lead to reduced food intake.
Professor Sadaf Farooqi at the Institute of Metabolic Science in Cambridge, UK, and colleagues identified 61 variants in the melanocortin 4 receptor, from analysing the genetics of half a million people in the UK Biobank.
These variants were checked against details of the participants’ body mass index and obesity-related cardiometabolic diseases.
This highlighted a subset of genetic variants that cause an increase in melanocortin 4 receptor function. These are linked to significantly lower body mass index and obesity, as well as type 2 diabetes and coronary artery disease, the researchers report.
Writing in Cell, they state that harnessing this pathway “may represent an effective strategy for weight loss and the treatment of obesity-related cardiometabolic diseases."
The team estimate that around four million people in the UK carry these genetic variants that protect them from obesity, type 2 diabetes and heart disease.
“This study drives home the fact that genetics plays a major role in why some people are obese – and that some people are fortunate enough to have genes that protect them from obesity,” said Professor Farooqi.
“It doesn’t mean that we can’t influence our weight by watching what we eat, but it does mean the odds are stacked against some people and in favour of others.”
Co-author Dr Luca Lotta added: “Our findings may pave the way for a new generation of weight loss therapies that activate melanocortin 4 receptor.”
Lotta, L. A. et al. Human gain-of-function MC4R variants show signaling bias and protect against obesity. Cell 18 April 2019; doi: 10.1016/j.cell.2019.03.044
Leave a Reply