Mice lacking the G protein gamma3-subunit show resistance to opioids and diet induced obesity.

Contributing to the obesity epidemic, there is increasing evidence that overconsumption of high-fat foods may be analogous to drug addiction in that the palatability of these foods is associated with activation of specific reward pathways in the brain. With this perspective, we report that mice lacking the G protein gamma(3)-subunit (Gng3(-/-) mice) show resistance to high-fat diet-induced weight gain over the course of a 12-wk study. Compared with Gng3(+/+) controls, female Gng3(-/-) mice exhibit a 40% reduction in weight gain and a 53% decrease in fat pad mass, whereas male Gng3(-/-) mice display an 18% reduction in weight gain and no significant decrease in fat pad mass.