THE UNCOUPLING PROTEIN, THERMOGENIN

The uncoupling protein (UCP) or thermogenin is a 33 kDa inner-membrane mitochondrial protein exclusive to brown adipocytes in mammals that f unctions as a proton transporter, allowing the dissipation as heat of the proton gradient generated by the respiratory chain and thereby unc oupling oxidative phosphorylation. Thermogenesis (heat production) in brown adipose tissue, which is activated in response to cold exposure or chronic overeating, depends largely on UCP activity. Norepinephrine , released from sympathetic terminals and acting via beta-adrenoceptor s and cAMP, is the main positive regulator of both UCP synthesis and a ctivity. Brown fat thermogenesis plays a critical role in thermoregula tion and in overall energy balance, at least in rodents. Manipulation of thermogenesis, whether through UCP or through analogous uncoupling proteins, could be an effective strategy against obesity. (C) 1998 Els evier Science Ltd. All rights reserved.