Tumor necrosis factor-alpha regulates in vivo expression of the rat UCP family differentially

A family of uncoupling proteins (UCPs), free fatty acid anion transporters, plays a crucial role in energy homeostatic thermoregulation, Tumor necrosi s 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 UCP s in thermogenesis, effects of TNF-alpha on rat UCP gene expression were ex amined in intrascapular brown adipose tissue (WAT), epididymal white adipos e tissue (WAT) and soleus muscle (Muscle). Administration of TNF-alpha elev ated rectal temperature by 0.7 degrees C as well as serum leptin which peak ed at 6 h, compared with saline controls. BAT UCP1 mRNA expression was incr eased 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, U CP2 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 treatme nt. UCP3 mRNA in Muscle, but not in BAT or WAT, was exclusively up-regulate d by 1.7-fold at 16 h after the treatment. These results indicate that TNF- alpha up-regulates UCP gene expression differentially and tissue dependentl y, and add novel insights into thermogenesis under conditions of malignancy and inflammation. (C) 1999 Elsevier Science B.V. All rights reserved.