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

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 o...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of clinical investigation 1998-10, Vol.102 (7), p.1345-1351
Main Authors: Argyropoulos, G, Brown, A M, Willi, S M, Zhu, J, He, Y, Reitman, M, Gevao, S M, Spruill, I, Garvey, W T
Format: Article
Language:English
Subjects:
Alternative Splicing
Base Sequence
Black or African American
Black People - genetics
Carrier Proteins - chemistry
Carrier Proteins - genetics
Codon, Terminator
Diabetes Mellitus - genetics
Diabetes Mellitus - metabolism
Diabetes Mellitus, Type 2 - genetics
Diabetes Mellitus, Type 2 - metabolism
Energy Metabolism - genetics
Ethnicity
Exons
Female
Genetic Carrier Screening
Humans
Ion Channels
Lipolysis - genetics
Male
Mitochondrial Proteins
Models, Molecular
Obesity
Oxygen Consumption - genetics
Pedigree
Point Mutation
Polymerase Chain Reaction
Polymorphism, Genetic
Protein Conformation
Sierra Leone
Uncoupling Protein 3
White People - genetics
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0021-9738
DOI:10.1172/jci4115