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. Leal; Rochelle Goldsmith; Antonio L. Andreu; Claudio Bruno; Salvatore DiMauro; Moonseong Heo; William L. Lowe; Bradford B. Lowell; David B. Allison; Rudolph L. Leibel

doi:10.2337/diabetes.48.9.1890

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 journal › Article › peer-review

50 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 language	English (US)
Pages (from-to)	1890-1895
Number of pages	6
Journal	Diabetes
Volume	48
Issue number	9
DOIs	https://doi.org/10.2337/diabetes.48.9.1890
State	Published - 1999
Externally published	Yes

ASJC Scopus subject areas

Internal Medicine
Endocrinology, Diabetes and Metabolism

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.2337/diabetes.48.9.1890

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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

Chung, WK, Luke, A, Cooper, RS, 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, Leal, SM, Goldsmith, R, Andreu, AL, Bruno, C, DiMauro, S, Heo, M, Lowe, WL, Lowell, BB, Allison, DB & Leibel, RL 1999, 'Genetic and physiologic analysis of the role of uncoupling protein 3 in human energy homeostasis', Diabetes, vol. 48, no. 9, pp. 1890-1895. https://doi.org/10.2337/diabetes.48.9.1890

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title = "Genetic and physiologic analysis of the role of uncoupling protein 3 in human energy homeostasis",

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.",

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doi = "10.2337/diabetes.48.9.1890",

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T1 - Genetic and physiologic analysis of the role of uncoupling protein 3 in human energy homeostasis

AU - Chung, Wendy K.

AU - Luke, Amy

AU - Cooper, Richard S.

AU - Rotini, Charles

AU - Vidal-Puig, Antonio

AU - Rosenbaum, Michael

AU - Chua, Melvin

AU - Solanes, Gemma

AU - Zheng, Min

AU - Zhao, Long

AU - LeDuc, Charles

AU - Eisberg, Andrew

AU - Chu, Florence

AU - Murphy, Ellen

AU - Schreier, Mindy

AU - Aronne, Louis

AU - Caprio, Sonia

AU - Kahle, Bowie

AU - Gordon, Derek

AU - Leal, Suzanne M.

AU - Goldsmith, Rochelle

AU - Andreu, Antonio L.

AU - Bruno, Claudio

AU - DiMauro, Salvatore

AU - Heo, Moonseong

AU - Lowe, William L.

AU - Lowell, Bradford B.

AU - Allison, David B.

AU - Leibel, Rudolph L.

PY - 1999

Y1 - 1999

N2 - 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.

AB - 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.

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JF - Diabetes

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ER -

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

Abstract

ASJC Scopus subject areas

UN SDGs

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