OBESITY RESEARCH CONTINUES TO SPRING LEAKS

Recent discoveries about the roles of 2 uncoupling proteins are changi ng the way we view obesity and its treatment. The author is also a coa uthor of a recent Nature report that mice deficient in uncoupling prot ein 1 (UCP1) did not become fat, as anticipated, but lean. She found t hat the other uncoupling protein (UCP2) was up-regulated in the brown adipose tissue (BAT) of these mice, compensating, at least in part, fo r the lack of UCP1 and preventing obesity. Researchers have known for 40 years that the function of BAT is heat production. In 1978, researc hers discovered UCP1, the protein responsible for this function. Subse quent investigation focused on the role of this protein in staving off obesity in animal models. In the early 1990s, surprising evidence fro m tissues other than BAT show that 20% to 40% of resting cellular ener gy expenditure is used to counter a proton leak down the electrochemic al gradient across the mitochondrial inner membrane. This leak was fou nd to be related to metabolic rate; the search for the mechanism of th e leak led to the discovery of UCP2. Both uncoupling proteins have bee n found to act as leaks in mitochondrial inner membranes, allowing the dissipation of proton motive force. These findings could lead to new treatments for obesity and non-insulin-dependent diabetes mellitus.