UNCOUPLING PROTEIN-2 - A NOVEL GENE LINKED TO OBESITY AND HYPERINSULINEMIA

A mitochondrial protein called uncoupling protein (UCP1) plays an impo rtant role in generating heat and burning calories by creating a pathw ay that allows dissipation of the proton electrochemical gradient acro ss the inner mitochondrial membrane in brown adipose tissue, without c oupling to any other energy-consuming process(1). This pathway has bee n implicated in the regulation of body temperature, body composition a nd glucose metabolism(2). However, UCP1-containing brown adipose tissu e is unlikely to be involved in weight regulation in adult large-size animals and humans living in a thermoneutral environment (one where an animal does not have to increase expenditure to lose temperature), as there is little brown adipose tissue present(3). We now report the di scovery of a gene that codes for a novel uncoupling protein, designate d UCP2, which has 59% aminoacid identity to UCP1, and describe propert ies consistent with a role in diabetes and obesity. In comparison with UCP1, UCP2 has a greater effect on mitochondrial membrane potential w hen expressed in yeast. Compared to UCP1, the gene is widely expressed in adult human tissues, including tissues rich in macrophages, and it is upregulated in white fat in response to fat feeding. Finally, UCP2 maps to regions of human chromosome 11 and mouse chromosome 7 that ha ve been linked to hyperinsulinaemia and obesity. Our findings suggest that UCP2 has a unique role in energy balance, body weight regulation and thermoregulation and their responses to inflammatory stimuli.