Genetic and physiologic analysis of the role of uncoupling protein 3 in human energy homeostasis

Wendy K. Chung, Amy Luke, Richard S. Cooper, Charles Rotini, Antonio Vidal-Puig, Michael Rosenbaum, Melvin Chua, Gemma Solanes, Min Zheng, Long Zhao, Charles LeDuc, Andrew Eisberg, Florence Chu, Ellen Murphy, Mindy Schreier, Louis Aronne, Sonia Caprio, Bowie Kahle, Derek Gordon, Suzanne M. LealRochelle Goldsmith, Antonio L. Andreu, Claudio Bruno, Salvatore DiMauro, Moonseong Heo, William L. Lowe, Bradford B. Lowell, David B. Allison, Rudolph L. Leibel

Research output: Contribution to journalArticle

48 Scopus citations

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 Va19Met, 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.

Original languageEnglish (US)
Pages (from-to)1890-1895
Number of pages6
JournalDiabetes
Volume48
Issue number9
DOIs
StatePublished - Sep 11 1999

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Chung, W. K., Luke, A., Cooper, R. S., Rotini, C., Vidal-Puig, A., Rosenbaum, M., Chua, M., Solanes, G., Zheng, M., Zhao, L., LeDuc, C., Eisberg, A., Chu, F., Murphy, E., Schreier, M., Aronne, L., Caprio, S., Kahle, B., Gordon, D., ... Leibel, R. L. (1999). Genetic and physiologic analysis of the role of uncoupling protein 3 in human energy homeostasis. Diabetes, 48(9), 1890-1895. https://doi.org/10.2337/diabetes.48.9.1890