People living with obesity tend to have unhealthy glucose and lipid levels in their blood, as well as high blood pressure. As a result, they are more at risk of cardiovascular and metabolic diseases. But scientists have observed that up to 45% of people living with obesity have healthy blood pressure and glucose and lipid levels, and therefore may not be at high risk of disease. The reason why this group of people with obesity remain healthy, has been poorly understood.

But now a team of researchers have identified a range of genes that are linked to both elevated levels of body fat, as well as offering protection from some of the negative health impacts of obesity. The results were published in the journal Nature Metabolism.

"The identified genes seem to benefit our health by helping to maintain a healthy fat tissue. Some of the genes may offer targets for the development of new therapies that lower the risk of diabetes and heart disease by improving the health of our fat tissue," says the author.

The scientists made the discovery by analyzing data from hundreds of thousands people who had been assessed for their body fat and disease risk markers. They identified 62 sections of the genome that were significantly associated with both high levels of body fat and lower risk of cardiometabolic diseases. Further analyses showed that the genes had a range of functions in the body, including the regulation and development of fat cells, distribution of body fat, as well as energy regulation and inflammation.

Genes prioritized in each locus support a key role of fat distribution (FAM13A, IRS1 and PPARG) and adipocyte function (ALDH2, CCDC92, DNAH10, ESR1, FAM13A, MTOR, PIK3R1 and VEGFB). Several additional mechanisms are involved as well, such as insulin–glucose signalling (ADCY5, ARAP1, CREBBP, FAM13A, MTOR, PEPD, RAC1 and SH2B3), energy expenditure and fatty acid oxidation (IGF2BP2), browning of white adipose tissue (CSK, VEGFA, VEGFB and SLC22A3) and inflammation (SH2B3, DAGLB and ADCY9). 

Staff Scientist Lam Opal Huang from CBMR carried out the computational analyses that identified the genes.

"We used a data-driven approach in this study, which led us to find new genes associated with fat tissue health, instead of the known obesity genes associated with central nervous system, which control satiety and are typically linked to unhealthy obesity," says the Staff Scientist.

https://cbmr.ku.dk/news/2020/genes-identified-that-increase-the-risk-of-obesity-but-also-protect-against-disease/

https://www.nature.com/articles/s42255-021-00346-2