A variation in a genetic region associated with obesity causes fat to be stored rather than burned.

Melina Claussnitzer at the Beth Israel Deaconess Medical Center in Boston, Massachusetts, Manolis Kellis at the Massachusetts Institute of Technology in Cambridge and their colleagues studied fat cells from 52 people with a version of the FTO genetic region that is associated with obesity and from 48 people with the non-risk version. The team found a single-nucleotide change in the risk-associated FTO region that boosted expression of the genes IRX3 and IRX5, which decreased the amount of energy burned and dissipated as heat. In fat precursor cells, this change resulted in the development of more energy-storing white fat cells and fewer energy-burning beige fat cells.

Inhibiting Irx3 in mice caused the animals to lose weight without a change in appetite or exercise.

N. Engl. J. Med. http://doi.org/6z5 (2015)