Diabetes Protection, Favorable Fat Features Linked to Liver Gene Mutations in Exome Study

In Nature Communications, researchers from the Regeneron Genetics Center and other centers in the US, Sweden, Italy, Mexico, and the UK describe rare coding variants in a liver-expressed gene called INHBE that appear to not only coincide with more favorable fat distribution and metabolic patterns, but also dial down the risk of developing type 2 diabetes (T2D). The team dug into exome sequences for 618,375 individuals from the UK, Sweden, and Mexico, focusing in on 16 fat distribution-associated genes. Calling body fat distribution "a major, heritable risk factor for cardiometabolic disease, independent of overall adiposity," the authors went on to more fully characterize predicted protein-truncating changes to the circulating growth factor gene INHBE, demonstrating that the inhibin beta-E protein it encodes can impact fat storage and the risk of related downstream conditions such as T2D. "Our results suggest that blocking inhibin beta-E may be a therapeutic approach for promoting metabolic health," they write, "and uncover biological interplays between liver and adipose tissue in energy storage."