Early development of lipogenesis in genetically obese (ob/ob) mice

This study was designed to sequence the earliest metabolic abnormalities associated with the development of obesity in the obese hyperglycemic mouse (C57BL/6J ob/ob). In situ lipogenesis was measured with 3H2O in fetuses at day 19 of gestation and in 5-, 10-, 15-, and 35-day-old mice. Preobese 15-day-old animals were identified on the basis of rectal hypothermia. The earliest increased accumulation of fatty acids was observed in the carcass of 15-day-old preobese animals (ob/ob) compared to their lean littermates (+/?) and known lean controls (+/+). The increased carcass lipogenesis in these animals was accompanied by an increase in plasma insulin concentration. Weaned 35-day-old obese animals showed a significant increase in hepatic and subcutaneous adipose tissue lipogenesis, plasma insulin, and glucose values when compared to their littermates (+/?). The results indicate that increased carcass lipogenesis, hyperinsulinemia, and hypothermia appear between days 10 and 15 and that these abnormalities precede the hyperglycemia and increased hepatic lipogenesis observed in the mature ob/ob mice.