OBESITY GENES - BENEFICIAL-EFFECTS IN HETEROZYGOUS MICE

The mouse mutant genes obese (ob) and diabetes (db) cause similar obesity-diabetes states in homozygotes. These obesity syndromes are characterized by a more efficient conversion of food to lipid and a slower rate of catabolism on fasting. Heterozygous mice, either ob/+ or db/+, survived a prolonged fast significantly longer than normal homozygotes (+/+); this suggests that the heterozygotes exhibited increased metabolic efficiency, a feature normally associated with both homozygous mutants. The existence of this thriftiness trait, if manifested by heterozygous carriers in wild populations, would lend credence to the thrifty gene concept of diabetes. Beneficial effects of normally deleterious genes may have played a role in the development of diabetes-susceptible human populations and may have provided the survival advantage that allowed both the development and successful establishment of species in desert and other less affluent regions.