Effects of butyrate on ouabain-sensitive respiration of hamster brown adipocytes

Brown adipose tissue is an important site of cold-induced nonshivering thermogenesis in many mammals. The plasma membrane-bound Na+-K+-ATPase has been shown to be significantly involved in this thermogenesis although its exact role is unknown at present. Evidence that coupling of oxidative phosphorylation to electron transport may become loosened during thermogenesis has prompted an investigation of potential roles of the Na+-K+ pump that would be compatible with altered respiratory coupling. One such role is that of modulating norepinephrine (NE)-induced lipolysis and hence provision of free fatty acids to the mitochondria. Under such conditions, inhibition of the pump would reduce NE-induced respiration by limiting substrate availability. If, in fact, the primary role of the pump in NE-induced thermogenesis is to facilitate substrate availability, provision of exogenous substrate should bypass this involvement and ameliorate the ouabain inhibition of respiration. In the present study, this possibility was examined by determining the effect of an exogenous substrate, butyrate, on the contribution of the Na+-K+ pump to NE-stimulated respiration of isolated hamster brown adipocytes. Although exogenous butyrate was able to serve as a substrate for brown adipocyte respiration, its presence had no significant effect on the ouabain sensitivity of NE-induced rates of oxygen consumption. That is, ouabain (1 mM) inhibited the NE-evoked thermogenesis of the adipocytes by 77.7 +/- 6.5% in the absence of butyrate (2 mM) and by 73.4 +/- 9.9% in its presence. It appears, therefore, that the contribution of the Na+-K+ membrane pump to brown fat thermogenesis does not simply reflect modulation of NE-evoked lipolysis.