UNCOUPLING PROTEIN-3 - A MUSCLE-SPECIFIC GENE UP-REGULATED BY LEPTIN IN OB OB MICE/

We identified and partially characterized another member of the uncoup ling protein termed UCP3. Human and mouse UCP3 protein sequences are 8 6% identical to each other, and 73% and 59% identical to UCP2 and UCP1 , respectively. Expression of human UCP3 in yeast resulted in a drasti c decrease of mitochondria membrane potential. Northern analysis showe d that UCP3 was highly expressed in skeletal muscle in human, rat, and mouse. Mapping of UCP3 placed it to the same chromosomal region of UC P2 in both human and mouse, a region that is linked to obesity and hyp erinsulinemia. Furthermore, adenovirus-mediated leptin expression in o bese ob/ob mice led to increased expression of UCP3 in skeletal muscle . The data indicate that UCP3 encodes a muscle-specific uncoupling pro tein that may play an important role in the regulation of energy expen diture and development of obesity. (C) 1998 Elsevier Science B.V.