Involvement of thyroid hormones in the effect of intracerebroventricular leptin infusion on uncoupling protein-3 expression in rat muscle

We have shown previously that continuous (6 days) intracerebroventricular ( ICV) leptin infusion in normal rats resulted in decreases in food intake an d body weight. A reduction of food intake imposed on control rats (pair-fee ding), aimed at mimicking leptin-induced hyperphagia, produced a marked dec rease in the expression of muscle uncoupling protein-3 (UCP-3), whereas ICV infusion of leptin prevented such a decrease in UCP-3. To investigate an i nvolvement of thyroid hormones in this effect of leptin, plasma levels of t hese hormones were determined in ICV leptin-infused, ICV vehicle-infused ad libitum fed or pair-fed controls. ICV leptin infusion and pair-feeding res ulted in decreased plasma thyroid-stimulating hormone (TSH) and T4 levels r elative to ad libitum fed controls. ICV leptin infusion maintained plasma l evels of T3, but the levels were decreased by pair-feeding. The activity of the enzyme (hepatic 5'-monodeiodinase) responsible for T4/T3 conversion wa s measured. In the leptin-infused group, the activity of 5'-monodeiodinase was maintained at the values measured in ad libitum fed rats; in pair-fed r ats, activity was reduced. Thus, conversion of T4 to T3 is decreased by pai r-feeding, whereas such is not the case during leptin infusion. To further substantiate an involvement of thyroid hormones in the effect of leptin on muscle UCP-3 expression, hypothyroid rats were ICV infused with leptin or v ehicle. It was observed that in hypothyroid rats, ICV leptin was unable to maintain muscle UCP-3 expression at values measured in ad libitum fed contr ols. These results suggest that central leptin stimulates T3 production via an activation of T4 to T3 conversion, and that this stimulation could be r esponsible for the effect of leptin on muscle UCP-3 expression. Thyroid hor mones could thus be important mediators of the effect of leptin on energy e xpenditure.