CHRONIC CENTRAL LEPTIN INFUSION ENHANCES INSULIN-STIMULATED GLUCOSE-METABOLISM AND FAVORS THE EXPRESSION OF UNCOUPLING PROTEINS

Continuous (4 days) intracerebroventricular leptin infusion (12 mu g/d ay) was performed in lean rats, and its hormonometabolic effects mere determined. Intracerebroventricular leptin administration did not resu lt in leakage of the hormone into the peripheral circulation. Thus, it s effects were elicited by its presence within the central nervous sys tem. Intracerebroventricular leptin infusion produced marked decreases in food intake and body weight gain relative to vehicle-infused fed a d libitum rats. Because decreases in food intake alter hormonometaboli c homeostasis, additional control rats pair-fed to the amount of food consumed by leptin-infused ones mere included in the study. Intracereb roventricular leptin-infused and vehicle-infused pair-fed rats were ch aracterized, relative to vehicle-infused ad libitum-fed animals, by de creases in body weight and insulinemia and by increases in insulin-sti mulated overall glucose utilization and muscle and brown adipose tissu e glucose utilization index. Brown adipose tissue uncoupling protein ( UCP)1, UCP2, and UCP3 mRNA levels were markedly decreased in pair-fed animals relative to those of fed ad libitum control animals, as mere L iver and white adipose tissue UCP2 and muscle UCP3 mRNA levels. In mar ked contrast, intracerebroventricular leptin administration was accomp anied by the maintenance of high UCP1, UCP2, and UCP3 expression in al l these tissues. Thus, despite analogies between leptin's effects and those of pair-feeding with regard to glucose handling, their respectiv e underlying mechanisms differ, While leptin maintains or favors energ y-dissipating mechanisms (UCP1, UCP2, and UCP3), the latter are marked ly depressed in pair-fed rats. This effect of leptin may prevent subse quent excessive storage processes, thereby maintaining normal body hom eostasis.