Costford et al. The effect was observed both when mice were fed with a standard diet or with a high fat diet Senese et al. Importantly, these findings have been recently confirmed through a meta-analysis showing an association of the polymorphism with protection from obesity in a European patient population de Almeida Brondani et al. Heterozygous individuals that have a missense GA polymorphism show decreased whole body fat oxidation compared to controls Argyropoulos et al.
They also present reduced levels of plasma lactate Adams et al. Children carrying these mutations exhibited a higher percentage of fat and BMI, which was associated with dyslipidemia and lower insulin sensitivity Musa et al. The uncoupling proteins have several hypothesized functions including thermogenesis in certain tissues, protection from ROS, mediation of fatty acids oxidation and export of fatty acids, which are all related to the above pathologies. Hence, an understanding of the mitochondrial processes that lead to uncoupling and, in particular, the elucidation of the exact role played by UCPs at the mitochondrial level and in EM may provide an attractive therapeutic target for diseases rooted in metabolic imbalance.
Recent evidence, indicating that brown and beige adipocyte can be recruited by different stimuli, raises the possibility that they may represent separate and distinct targets for therapeutic intervention. Although the roles of UCP 3 are not completely clear, current data in human subjects living at thermoneutrality suggest a possible involvement of this protein in EM as well as in counteracting obesity, insulin resistance, and T2DM Figure 2.
Therefore, UCP 1 and UCP 3 represent promising therapeutic targets for treating pathologies that result from energy unbalance. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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Permissions Icon Permissions. All rights reserved. For permissions, please e-mail: journals. Issue Section:. You do not currently have access to this article. There are still fundamental uncertainties about their transport mechanism, and thus they have been proposed to transport fatty acids, protons or superoxide ions.
Are all UCPs 'true' uncoupling proteins, or are some of them metabolite carriers? How are these transporters organized so that they can readily switch from carrier mode to channel mode? No high-resolution structural data are yet available for any member of the mitochondrial carrier superfamily, and when this information becomes available it could prove a turning point in understanding the molecular basis of the transport mechanism, specificity and regulation of UCPs.
The scientific interest in this protein family can be easily understood. At the cellular level, their role in the control of ATP levels, redox balance, oxidative stress and apoptosis shows their importance. Disturbances in UCP function could underlie pathological states such as obesity, diabetes, inflammatory processes or cancer cachexia. Development of drugs that modulate the activity of the UCPs could one day become a new strategy for the treatment of these pathologies.
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You can also search for this author in PubMed Google Scholar. Correspondence to Eduardo Rial. Reprints and Permissions. Ledesma, A. The mitochondrial uncoupling proteins. Genome Biol 3, reviews Download citation. Published : 29 November Anyone you share the following link with will be able to read this content:.
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