Genetic and physiologic analysis of the role of uncoupling protein 3 in human energy homeostasis.
Diabetes
; 48(9): 1890-5, 1999 Sep.
Article
em En
| MEDLINE
| ID: mdl-10480626
ABSTRACT
By virtue of its potential effects on rates of energy expenditure, uncoupling protein 3 (UCP3) is an obesity candidate gene. We identified nine sequence variants in UCP3, including Val9Met, Val102Ile, Arg282Cys, and a splice site mutation in the intron between exons 6 and 7. The splice mutation results in an inability to synthesize mRNA for the long isoform (UCP3L) of UCP3. Linkage (sib pair), association, and transmission disequilibrium testing studies on 942 African-Americans did not suggest a significant effect of UCP3 on body composition in this group. In vastus lateralis skeletal muscle of individuals homozygous for the splice mutation, no UCP3L mRNA was detectable; the short isoform (UCP3S) was present in an increased amount. In this muscle, we detected no alterations of in vitro mitochondrial coupling activity, mitochondrial respiratory enzyme activity, or systemic oxygen consumption or respiratory quotient at rest or during exercise. These genetic and physiologic data suggest the following possibilities UCP3S has uncoupling capabilities equivalent to UCP3L; other UCPs may compensate for a deficiency of bioactive UCP3L; UCP3L does not function primarily as a mitochondrial uncoupling protein.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Transporte
/
População Negra
/
Metabolismo Energético
/
Mitocôndrias
Tipo de estudo:
Clinical_trials
Limite:
Humans
Idioma:
En
Revista:
Diabetes
Ano de publicação:
1999
Tipo de documento:
Article
País de afiliação:
Estados Unidos