Cusin I, Rouru J, Visser T, Burger A G, Rohner-Jeanrenaud F
Division of Endocrinology and Diabetology, Geneva University, Faculty of Medicine, Switzerland.
Diabetes. 2000 Jul;49(7):1101-5. doi: 10.2337/diabetes.49.7.1101.
We have shown previously that continuous (6 days) intracerebroventricular (ICV) leptin infusion in normal rats resulted in decreases in food intake and body weight. A reduction of food intake imposed on control rats (pair-feeding), aimed at mimicking leptin-induced hyperphagia, produced a marked decrease 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 involvement of thyroid hormones in this effect of leptin, plasma levels of these hormones were determined in ICV leptin-infused, ICV vehicle-infused ad libitum fed or pair-fed controls. ICV leptin infusion and pair-feeding resulted in decreased plasma thyroid-stimulating hormone (TSH) and T4 levels relative to ad libitum fed controls. ICV leptin infusion maintained plasma levels of T3, but the levels were decreased by pair-feeding. The activity of the enzyme (hepatic 5'-monodeiodinase) responsible for T4/T3 conversion was 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 rats, activity was reduced. Thus, conversion of T4 to T3 is decreased by pair-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 vehicle. It was observed that in hypothyroid rats, ICV leptin was unable to maintain muscle UCP-3 expression at values measured in ad libitum fed controls. These results suggest that central leptin stimulates T3 production via an activation of T4 to T3 conversion, and that this stimulation could be responsible for the effect of leptin on muscle UCP-3 expression. Thyroid hormones could thus be important mediators of the effect of leptin on energy expenditure.
我们之前已经表明，在正常大鼠中连续6天脑室内（ICV）输注瘦素会导致食物摄入量和体重下降。对对照大鼠进行旨在模拟瘦素诱导的摄食减少的食物摄入量减少（配对喂养），会使肌肉解偶联蛋白3（UCP-3）的表达显著降低，而ICV输注瘦素可防止UCP-3的这种降低。为了研究甲状腺激素是否参与瘦素的这种作用，在ICV输注瘦素、ICV输注溶媒的随意进食或配对喂养的对照大鼠中测定了这些激素的血浆水平。与随意进食的对照相比，ICV输注瘦素和配对喂养导致血浆促甲状腺激素（TSH）和T4水平降低。ICV输注瘦素维持了T3的血浆水平，但配对喂养使其水平降低。测量了负责T4/T3转化的酶（肝脏5'-单脱碘酶）的活性。在输注瘦素的组中，5'-单脱碘酶的活性维持在随意进食大鼠中测得的值；在配对喂养的大鼠中，活性降低。因此，配对喂养会降低T4向T3的转化，而在输注瘦素期间则不会。为了进一步证实甲状腺激素参与瘦素对肌肉UCP-3表达的作用，对甲状腺功能减退的大鼠ICV输注瘦素或溶媒。观察到在甲状腺功能减退的大鼠中，ICV输注瘦素无法将肌肉UCP-3表达维持在随意进食对照中测得的值。这些结果表明，中枢瘦素通过激活T4向T3的转化来刺激T3的产生，并且这种刺激可能是瘦素对肌肉UCP-3表达作用的原因。因此，甲状腺激素可能是瘦素对能量消耗作用的重要介质。
