Effects of mutations in the human uncoupling protein 3 gene on the respiratory quotient and fat oxidation in severe obesity and type 2 diabetes. (original) (raw)

Research Article Free access | 10.1172/JCI4115

A M Brown, S M Willi, J Zhu, Y He, M Reitman, S M Gevao, I Spruill, and W T Garvey

Department of Medicine, Division of Endocrinology, Medical University of South Carolina, 29425, USA. argyrog@musc.edu

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Department of Medicine, Division of Endocrinology, Medical University of South Carolina, 29425, USA. argyrog@musc.edu

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Department of Medicine, Division of Endocrinology, Medical University of South Carolina, 29425, USA. argyrog@musc.edu

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Department of Medicine, Division of Endocrinology, Medical University of South Carolina, 29425, USA. argyrog@musc.edu

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Department of Medicine, Division of Endocrinology, Medical University of South Carolina, 29425, USA. argyrog@musc.edu

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Department of Medicine, Division of Endocrinology, Medical University of South Carolina, 29425, USA. argyrog@musc.edu

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Department of Medicine, Division of Endocrinology, Medical University of South Carolina, 29425, USA. argyrog@musc.edu

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Department of Medicine, Division of Endocrinology, Medical University of South Carolina, 29425, USA. argyrog@musc.edu

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Department of Medicine, Division of Endocrinology, Medical University of South Carolina, 29425, USA. argyrog@musc.edu

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Published October 1, 1998 -More info

Published October 1, 1998 -Version history

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Abstract

Human uncoupling protein 3 (UCP3) is a mitochondrial transmembrane carrier that uncouples oxidative ATP phosphorylation. With the capacity to participate in thermogenesis and energy balance, UCP3 is an important obesity candidate gene. A missense polymorphism in exon 3 (V102I) was identified in an obese and diabetic proband. A mutation introducing a stop codon in exon 4 (R143X) and a terminal polymorphism in the splice donor junction of exon 6 were also identified in a compound heterozygote that was morbidly obese and diabetic. Allele frequencies of the exon 3 and exon 6 splice junction polymorphisms were determined and found to be similar in Gullah-speaking African Americans and the Mende tribe of Sierra Leone, but absent in Caucasians. Moreover, in exon 6-splice donor heterozygotes, basal fat oxidation rates were reduced by 50%, and the respiratory quotient was markedly increased compared with wild-type individuals, implicating a role for UCP3 in metabolic fuel partitioning.

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