Uncoupling Proteins: Functional Characteristics and Role in the Pathogenesis of Obesity and Type II Diabetes
Diabetologia 2001) 44: 946±965 Ó Springer-Verlag 2001 Uncoupling proteins: functional characteristics and role in the pathogenesis of obesity and Type II diabetes L. T.Dalgaard, O.Pedersen Steno Diabetes Center, Gentofte, Denmark Abstract obesity. The three uncoupling protein homologue genes UCP1, UCP2, and UCP3 have been investigat- Uncoupling proteins are mitochondrial carrier pro- ed for polymorphisms and mutations and their impact teins which are able to dissipate the proton gradient on Type II diabetes mellitus, obesity, and body weight of the inner mitochondrial membrane. This uncou- gain or BMI. The main conclusion is that variation in pling process reduces the amount of ATP generated the UCP1, UCP2 or UCP3 genes is not associated through an oxidation of fuels. The hypothesis that un- with major alterations of body weight gain. The con- coupling proteins UCPs) are candidate genes for hu- tribution of UCP genes towards polygenic obesity man obesity or Type II non-insulin-dependent) dia- and Type II diabetes is evaluated and discussed. [Dia- betes mellitus is based on the finding that a chemical betologia 2001) 44: 946±965] uncoupling of the mitochondrial membrane reduces body adiposity, and that lower metabolic rates predict Keywords Uncoupling proteins, Type II diabetes weight gain. It is straightforward to hypothesize that mellitus, obesity, genetics, body weight regulation, common polymorphisms of UCP1, UCP2 and UCP3 energy expenditure, metabolic rate, brown adipose genes lower metabolic rate by a more efficient energy tissue, white adipose tissue, reactive oxygen species, coupling in the mitochondria. Furthermore, geneti- polymorphism, mutation, transgenics, gene knock- cally engineered mice over expressing different UCP out.
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