Obesity research continues to spring leaks.
Recent discoveries about the roles of 2 uncoupling proteins are changing the way we view obesity and its treatment. The author is also a coauthor of a recent Nature report that mice deficient in uncoupling protein 1 (UCP1) did not become fat, as anticipated, but lean. She found that the other uncoupling protein (UCP2) was up-regulated in the brown adipose tissue (BAT) of these mice, compensating, at least in part, for the lack of UCP1 and preventing obesity. Researchers have known for 40 years that the function of BAT is heat production. In 1978, researchers discovered UCP1, the protein responsible for this function. Subsequent investigation focused on the role of this protein in staving off obesity in animal models. In the early 1990s, surprising evidence from tissues other than BAT show that 20% to 40% of resting cellular energy expenditure is used to counter a proton leak down the electrochemical gradient across the mitochondrial inner membrane. This leak was found to be related to metabolic rate; the search for the mechanism of the leak led to the discovery of UCP2. Both uncoupling proteins have been 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.
Harper
M E
ME
Faculty of Medicine, University of Ottawa, Ont. mharper@uottawa.ca
D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D004734:Energy Metabolism; D006801:Humans; D007473:Ion Channels; D008565:Membrane Proteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins; D009765:Obesity / Q000378:metabolism / Q000628:therapy; D011506:Proteins / Q000378:metabolism*; D011522:Protons; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2
D002352:Carrier Proteins; D007473:Ion Channels; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D011522:Protons; C000604371:UCP1 protein, human; C000604389:UCP2 protein, human; C000604372:Ucp1 protein, mouse; C000604390:Ucp2 protein, mouse; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2