The uncoupling protein family and energy expenditure

Obesity may be the most common intractable disease in the United States. Although diets can temporarily reduce weight, the great majority of overweight adults will remain overweight throughout life. Five-year remission rates for people who successfully complete weight loss programs are less than 5%. Changes in body weight are controlled by the energy balance equation: energy intake - energy expenditure = weight change. Specific mechanisms controlling energy expenditure may have important medical implications, since individual variations of energy expenditure could promote or inhibit development of obesity. Furthermore, understanding of the regulation of energy balance will provide new therapeutic regimens, including regulated genes, that may be good drug therapy targets. This review describes a new class of mitochondrial proteins that partially uncouple the proton gradient from adenosine triphosphate synthesis. Thus, increased activity of these uncoupling proteins (UCPs) could increase calorie expenditure. There are three published members of the UCP family: UCP1, UCP2 and UCP3. They share some structural elements and they all partially uncouple mitochondrial respiration, but they vary greatly in tissue distribution and regulation. The UCPs probably have different physiological roles and vary in potential value for drug targeting of obesity.