Journal article
Mitochondrial energetics in the heart in obesity-related diabetes : Direct evidence for increased uncoupled respiration and activation of uncoupling proteins
Diabetes (New York, N.Y.), Vol.56(10), pp.2457-2466
2007
DOI: 10.2337/db07-0481
PMID: 17623815
Abstract
OBJECTIVE—In obesity and diabetes, myocardial fatty acid utilization and myocardial oxygen consumption (MVo2) are increased, and cardiac efficiency is reduced. Mitochondrial uncoupling has been proposed to contribute to these metabolic abnormalities but has not been directly demonstrated. RESEARCH DESIGN AND METHODS—Oxygen consumption and cardiac function were determined in db/db hearts perfused with glucose or glucose and palmitate. Mitochondrial function was determined in saponin-permeabilized fibers and proton leak kinetics and H2O2 generation determined in isolated mitochondria. RESULTS—db/db hearts exhibited reduced cardiac function and increased MVo2. Mitochondrial reactive oxygen species (ROS) generation and lipid and protein peroxidation products were increased. Mitochondrial proliferation was increased in db/db hearts, oxidative phosphorylation capacity was impaired, but H2O2 production was increased. Mitochondria from db/db mice exhibited fatty acid–induced mitochondrial uncoupling that is inhibitable by GDP, suggesting that these changes are mediated by uncoupling proteins (UCPs). Mitochondrial uncoupling was not associated with an increase in UCP content, but fatty acid oxidation genes and expression of electron transfer flavoproteins were increased, whereas the content of the F1 α-subunit of ATP synthase was reduced. CONCLUSIONS—These data demonstrate that mitochondrial uncoupling in the heart in obesity and diabetes is mediated by activation of UCPs independently of changes in expression levels. This likely occurs on the basis of increased delivery of reducing equivalents from β-oxidation to the electron transport chain, which coupled with decreased oxidative phosphorylation capacity increases ROS production and lipid peroxidation.
Details
- Title: Subtitle
- Mitochondrial energetics in the heart in obesity-related diabetes : Direct evidence for increased uncoupled respiration and activation of uncoupling proteins
- Creators
- Sihem BOUDINA - Division of Endocrinology, Metabolism, and Diabetes and Program in Human Molecular Biology and Genetics, University of Utah School of Medicine, Salt Lake City, Utah, United StatesSandra SENA - Division of Endocrinology, Metabolism, and Diabetes and Program in Human Molecular Biology and Genetics, University of Utah School of Medicine, Salt Lake City, Utah, United StatesE. Dale ABEL - Division of Endocrinology, Metabolism, and Diabetes and Program in Human Molecular Biology and Genetics, University of Utah School of Medicine, Salt Lake City, Utah, United StatesHeather THEOBALD - Division of Endocrinology, Metabolism, and Diabetes and Program in Human Molecular Biology and Genetics, University of Utah School of Medicine, Salt Lake City, Utah, United StatesXiaoming Sheng - Department of Family and Preventive Medicine, University of Utah School of Medicine, Salt Lake City, Utah, United StatesJordan J WRIGHT - Division of Endocrinology, Metabolism, and Diabetes and Program in Human Molecular Biology and Genetics, University of Utah School of Medicine, Salt Lake City, Utah, United StatesXia Xuan Hu - Division of Endocrinology, Metabolism, and Diabetes and Program in Human Molecular Biology and Genetics, University of Utah School of Medicine, Salt Lake City, Utah, United StatesSalwa AZIZ - Division of Endocrinology, Metabolism, and Diabetes and Program in Human Molecular Biology and Genetics, University of Utah School of Medicine, Salt Lake City, Utah, United StatesJosie I JOHNSON - Division of Endocrinology, Metabolism, and Diabetes and Program in Human Molecular Biology and Genetics, University of Utah School of Medicine, Salt Lake City, Utah, United StatesHeiko BUGGER - Division of Endocrinology, Metabolism, and Diabetes and Program in Human Molecular Biology and Genetics, University of Utah School of Medicine, Salt Lake City, Utah, United StatesVlad G ZAHA - Division of Endocrinology, Metabolism, and Diabetes and Program in Human Molecular Biology and Genetics, University of Utah School of Medicine, Salt Lake City, Utah, United States
- Resource Type
- Journal article
- Publication Details
- Diabetes (New York, N.Y.), Vol.56(10), pp.2457-2466
- Publisher
- American Diabetes Association; Alexandria, VA
- DOI
- 10.2337/db07-0481
- PMID
- 17623815
- ISSN
- 0012-1797
- eISSN
- 1939-327X
- Language
- English
- Date published
- 2007
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Biochemistry and Molecular Biology; Internal Medicine
- Record Identifier
- 9984025279902771
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