Effects of intravenously infused leptin on insulin sensitivity and on the expression of uncoupling proteins in brown adipose tissue

Centrally administered leptin has been shown to increase insulin-stimulated glucose utilization and to favor the expression of uncoupling proteins (UC Ps). To study if leptin also has direct peripherally mediated effects on th ese processes, this hormone (1 mg/day) or its vehicle was infused iv for 4 days to lean rats and insulin-stimulated glucose utilization in skeletal mu scle and adipose tissue as well as the expression of UCP messenger RNAs (mR NAs) in brown adipose tissue were measured. Iv leptin administration result ed in decreases in food intake (31%), body weight gain, and plasma insulin levels (45%), in increases in overall (23%) as well as brown adipose tissue and muscle glucose utilization, and in decreases in white adipose tissue g lucose uptake. Most of these changes were mimicked, in control rats, by giv ing them the same amount of food as that consumed by the leptin-infused gro up (pair-feeding). Iv leptin infusion also favored the expression of UCPs i n brown adipose tissue, either by increasing their expression or preventing the fall occurring during the pair-feeding regimen. Relative UCP expressio n levels were 100, 104, and 33 for UCP1, 100, 191, and 125 for UCP2 and 100 , 107, and 29 for UCP3 in ad libitum fed control rats, in leptin-treated ra ts and in pair-fed control rats, respectively. These results suggest that t he overall effect of leptin on glucose utilization and on the expression of UCPs may be mediated through central mechanism.