Induction of uncoupling protein expression in brown and white adipose tissue by leptin

Deposition of excess body fat occurs when energy intake chronically exceeds energy expenditure, In ob/ob mice, the absence of leptin affects both comp onents of the energy balance equation, and the mice become morbidly obese a fter weaning. Treatment of ob/ob mice with exogenous leptin reduces body we ight by decreasing food intake and stimulating energy utilization, but even when saline- and leptin-injected ob/ob mice are pair-fed, mice receiving l eptin lose significantly more weight. Therefore, the purpose of the present study was to test the hypotheses that uncoupling protein-1 (UCP1) expressi on is reduced in adipose tissue from ob/ob mice and is restored by treatmen t with exogenous leptin. Lean and ob/ob mice (5-6 weeks old) were housed at 23 C and treated with leptin (20 mu g/g BW.day) for 3 days before they wer e killed. Compared with levels in lean littermates, UCP1 messenger RNA (mRN A) and protein levels were lower in brown adipose tissue (BAT) and retroper itoneal white adipose tissue (WAT) from ob/ob mice. Treatment of ob/ob mice with leptin reduced body weight and produced a 4- to 5-fold increase in UC P1 mRNA levels in both interscapular BAT and retroperitoneal WAT. The incre ases in UCP1 mRNA were accompanied by comparable increases in UCP1 protein in mitochondrial preparations from each tissue. Given that the sole known f unction of UCP1 is to uncouple oxidative phosphorylation, the present resul ts are consistent with the conclusion that leptin stimulates energy utiliza tion in ob/ob mice by increasing thermogenic activity and capacity (UCP1). In addition, the present results suggest that decreased UCP1 expression in BAT and WAT of ob/ob mice is in part responsible for their increased metabo lic efficiency and propensity to become obese.