Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia

ABSTRACT A mitochondrial protein called uncoupling protein (UCP1) plays an important role in generating heat and burning calories by creating a pathway that allows dissipation of the proton

electrochemical gradient across the inner mitochondrial membrane in brown adipose tissue, without coupling to any other energy-consuming process1. This pathway has been implicated in the

regulation of body temperature, body composition and glucose metabolism2. However, UCP1-containing brown adipose tissue is unlikely to be involved in weight regulation in adult large-size

animals and humans living in a thermoneutral environment (one where an animal does not have to increase oxygen consumption or energy expenditure to lose or gain heat to maintain body

temperature), as there is little brown adipose tissue present3. We now report the discovery of a gene that codes for a novel uncoupling protein, designated UCP2, which has 59% amino-acid

identity to UCP1, and describe properties consistent with a role in diabetes and obesity. In comparison with UCP1, UCP2 has a greater effect on mitochondrial membrane potential when

expressed in yeast. Compared to _UCP1_, the gene is widely expressed in adult human tissues, including tissues rich in macrophages, and it is upregulated in white fat in response to fat

feeding. Finally, _UCP2_ maps to regions of human chromosome 11 and mouse chromosome 7 that have been linked to hyperinsulinaemia and obesity. Our findings suggest that UCP2 has a unique

role in energy balance, body weight regulation and thermoregulation and their responses to inflammatory stimuli. Access through your institution Buy or subscribe This is a preview of

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31–35 (1979). Article  CAS  Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * CNRS/CEREMOD, 9, rue Jules Hetzel, 92190, Meudon, France Christophe Fleury, 

Serge Raimbault, Odette Champigny, Corinne Levi-Meyrueis, Frederic Bouillaud & Daniel Ricquier * Rowe Program in Genetics and Depts. of Pediatrics, Biological Chemistry and Medicine, UC

Davis, Davis, California, 95616, USA Maria Neverova, Michael F. Seldin & Craig H. Warden * Department of Psychiatry and Behavioral Sciences, the Sarah Stedman Nutrition Center and

Department of Pharmacology, Duke University Medical Center, Durham, North Carolina, 27710, USA Sheila Collins & Richard S. Surwit Authors * Christophe Fleury View author publications You

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Correspondence to Craig H. Warden. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Fleury, C., Neverova, M., Collins, S. _et al._ Uncoupling protein-2: a

novel gene linked to obesity and hyperinsulinemia. _Nat Genet_ 15, 269–272 (1997). https://doi.org/10.1038/ng0397-269 Download citation * Received: 22 November 1996 * Accepted: 14 January

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