Masaki T, Yoshimatsu H, Chiba S, Hidaka S, Tajima D, Kakuma T, Kurokawa M, Sakata T
Department of Internal Medicine 1, School of Medicine, Oita Medical University, Japan.
Biochim Biophys Acta. 1999 Jan 4;1436(3):585-92. doi: 10.1016/s0005-2760(98)00173-8.
A family of uncoupling proteins (UCPs), free fatty acid anion transporters, plays a crucial role in energy homeostatic thermoregulation. Tumor necrosis factor-alpha (TNF-alpha), a member of the cytokine family, is well known as an endogenous pyrogen. To evaluate the interaction of TNF-alpha with UCPs in thermogenesis, effects of TNF-alpha on rat UCP gene expression were examined in intrascapular brown adipose tissue (BAT), epididymal white adipose tissue (WAT) and soleus muscle (Muscle). Administration of TNF-alpha elevated rectal temperature by 0.7 degree C as well as serum leptin which peaked at 6 h, compared with saline controls. BAT UCP1 mRNA expression was increased by 1.2-fold at 6 h after the TNF-alpha treatment and decreased by 0.8-fold at 16 h after the treatment. In contrast to UCP1 expression in BAT, UCP2 mRNA expressions in BAT, WAT, and Muscle was increased to reach maximum levels of 1.3-, 1.6- and 1.8-fold, respectively, at 16 h after the treatment. UCP3 mRNA in Muscle, but not in BAT or WAT, was exclusively up-regulated by 1.7-fold at 16 h after the treatment. These results indicate that TNF-alpha up-regulates UCP gene expression differentially and tissue dependently, and add novel insights into thermogenesis under conditions of malignancy and inflammation.
解偶联蛋白（UCPs）家族作为游离脂肪酸阴离子转运体，在能量稳态体温调节中发挥着关键作用。细胞因子家族成员肿瘤坏死因子-α（TNF-α）是众所周知的内源性致热原。为了评估TNF-α与UCPs在产热过程中的相互作用，研究了TNF-α对大鼠肩胛间棕色脂肪组织（BAT）、附睾白色脂肪组织（WAT）和比目鱼肌（肌肉）中UCP基因表达的影响。与生理盐水对照组相比，注射TNF-α使直肠温度升高了0.7摄氏度，血清瘦素也在6小时达到峰值。TNF-α处理后6小时，BAT中UCP1 mRNA表达增加了1.2倍，处理后16小时下降了0.8倍。与BAT中UCP1的表达情况相反，处理后16小时，BAT、WAT和肌肉中UCP2 mRNA表达分别增加至最大水平的1.3倍、1.6倍和1.8倍。处理后16小时，仅肌肉中的UCP3 mRNA上调了1.7倍，BAT和WAT中未见上调。这些结果表明，TNF-α对UCP基因表达的上调具有差异性和组织依赖性，并为恶性肿瘤和炎症条件下的产热过程提供了新的见解。
