Increased metabolic efficiency in obese mutant mice.

Several different single gene mutations are known to cause similar diabetes-obesity syndromes in mice. Our studies with two mutations, obese (ob) and diabetes (db) have shown that each syndrome develops similarly. Symptoms include hyperinsulinemia, hyperglycemia, hyperphagia, diabetes, and obesity coupled with similar, and large increases, in the efficiency of food utilization. Even when maintained on 50 percent of normal food intake, mutants still become obese. This increase in metabolic efficiency has been suggested to be due to a failure of mutant mice to thermoregulate. Our studies indicate that any defect in thermoregulation is not severe enough to conserve sufficient calories to account for the large increase in metabolic efficiency observed in each mutant and the increased efficiency seen in mutants must be a result of other mechanisms. More critical studies in both normal and obese mice should lead to information defining the contribution of the many different potential energy saving mechanisms available.