LEPTIN INCREASES UNCOUPLING PROTEIN EXPRESSION AND ENERGY-EXPENDITURE

In ob/ob mice, leptin increases energy expenditure and sympathetic out flow to brown adipose tissue (BAT). To test whether the mechanism of i ncreased energy expenditure may involve increased thermogenesis in BAT , we acclimated normal rats to thermoneutrality for 2 wk followed by l eptin administration for 1 wk. Some rats were food restricted for 1 wk to the level of food consumption in the leptin-treated ad libitum-fed rats, and the same rats were both food restricted and administered le ptin for a second week. We examined oxygen consumption and uncoupling protein (UCP) expression in BAT. Leptin increased oxygen consumption a fter the 5th and 6th days in ad libitum-fed rats and after the 4th, 5t h, and 6th days in food-restricted rats. Leptin increased BAT UCP mRNA levels greater than twofold in both ad libitum-fed and food restricte d rats. These data demonstrate a leptin-induced increase in energy exp enditure in nonmutant rodents and suggest that one mechanism by which leptin increases energy expenditure is through increased thermogenesis in BAT, including increased expression of UCP.