Weigle D S, Selfridge L E, Schwartz M W, Seeley R J, Cummings D E, Havel P J, Kuijper J L, BeltrandelRio H
Department of Medicine, University of Washington, Harborview Medical Center, Seattle 98104, USA.
Diabetes. 1998 Feb;47(2):298-302. doi: 10.2337/diab.47.2.298.
The newly described uncoupling protein 3 (UCP3) may make an important contribution to thermogenesis in humans because of its high level of expression in skeletal muscle. Contrary to expectations, fasting, a condition that reduces resting energy expenditure, has been reported to increase UCP3 expression in muscle. We have confirmed that a 10-fold increase in UCP3 mRNA levels occurs in rat quadriceps muscle between 12 and 24 h of food removal. A less consistent twofold increase in muscle UCP2 mRNA levels was observed in animals fasted for up to 72 h. Administration of recombinant leptin to prevent a fall in circulating leptin levels did not eliminate the fasting-induced increase in quadriceps UCP3 expression. Administration of a high dose of glucocorticoid to fed animals to mimic the increase in corticosterone induced by fasting did not reproduce the increase in UCP3 expression observed in fasted animals. In contrast, elevation of circulating free fatty acid levels in fed animals by Intralipid plus heparin infusion caused significant increases in the UCP3/actin mRNA ratio compared with saline-infused fed controls in both extensor digitorum longus (2.01 +/- 0.34 vs. 0.68 +/- 0.11, P = 0.002) and soleus muscles (0.31 +/- 0.07 vs. 0.09 +/- 0.02, P = 0.014). We conclude that free fatty acids are a potential mediator of the increase in muscle UCP3 expression that occurs during fasting. This seemingly paradoxical induction of UCP3 may be linked to the use of free fatty acid as a fuel rather than an increased need of the organism to dissipate energy.
新发现的解偶联蛋白3（UCP3）可能对人类产热有重要作用，因为它在骨骼肌中高度表达。与预期相反，禁食这种会降低静息能量消耗的状态，据报道会增加肌肉中UCP3的表达。我们已经证实，在大鼠股四头肌中，禁食12至24小时后UCP3 mRNA水平会增加10倍。在禁食长达72小时的动物中，肌肉UCP2 mRNA水平有不太一致的两倍增加。给予重组瘦素以防止循环瘦素水平下降并不能消除禁食诱导的股四头肌UCP3表达增加。给进食的动物注射高剂量糖皮质激素以模拟禁食诱导的皮质酮增加，并未重现禁食动物中观察到的UCP3表达增加。相反，通过输注脂质乳剂加肝素使进食动物循环游离脂肪酸水平升高，与输注生理盐水的进食对照相比，在趾长伸肌（2.01±0.34对0.68±0.11，P = 0.002）和比目鱼肌（0.31±0.07对0.09±0.02，P = 0.014）中，UCP3/肌动蛋白mRNA比值均显著增加。我们得出结论，游离脂肪酸是禁食期间肌肉UCP3表达增加的潜在介质。这种看似矛盾的UCP3诱导可能与游离脂肪酸作为燃料的利用有关，而不是机体对能量耗散需求的增加。
