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Cited by 502Mitochondrial Function and PathologyCardiovascular Function and Risk FactorsCardiac Ischemia and Reperfusion

Reduced Mitochondrial Oxidative Capacity and Increased Mitochondrial Uncoupling Impair Myocardial Energetics in Obesity

Boudina, Sihem, Sena, Sandra, O’Neill, Brian T., Tathireddy, Prakash, Young, Martin E., Abel, E. Dale·2005·Circulation
DOI 10.1161/circulationaha.105.554360
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Abstract

Background— Obesity is a risk factor for cardiovascular disease and is strongly associated with insulin resistance and type 2 diabetes. Recent studies in obese humans and animals demonstrated increased myocardial oxygen consumption (MV̇ o 2 ) and reduced cardiac efficiency (CE); however, the underlying mechanisms remain unclear. The present study was performed to determine whether mitochondrial dysfunction and uncoupling are responsible for reduced cardiac performance and efficiency in ob/ob mice. Methods and Results— Cardiac function, MV̇ o 2 , mitochondrial respiration, and ATP synthesis were measured in 9-week-old ob/ob and control mouse hearts. Contractile function and MV̇ o 2 in glucose-perfused ob/ob hearts were similar to controls under basal conditions but were reduced under high workload. Perfusion of ob/ob hearts with glucose and palmitate increased MV̇ o 2 and reduced CE by 23% under basal conditions, and CE remained impaired at high workload. In glucose-perfused ob/ob hearts, mitochondrial state 3 respirations were reduced but ATP/O ratios were unchanged. In contrast, state 3 respiration rates were similar in ob/ob and control mitochondria from hearts perfused with palmitate and glucose, but ATP synthesis rates and ATP/O ratios were significantly reduced in ob/ob , which suggests increased mitochondrial uncoupling. Pyruvate dehydrogenase activity and protein levels of complexes I, III, and V were reduced in obese mice. Conclusions— These data indicate that reduced mitochondrial oxidative capacity may contribute to cardiac dysfunction in ob/ob mice. Moreover, fatty acid but not glucose-induced mitochondrial uncoupling reduces CE in obese mice by limiting ATP production and increasing MV̇ o 2 .

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Crossref · 10.1161/circulationaha.105.554360

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  • Some groups have reported cardiac hypertrophy in hearts of young ob/ob mice, while others have only observed this phenotype in older animals.

    “For example, while some groups have reported cardiac hypertrophy in hearts of young ob/ob mice (30, 34, 227), others have only observed this phenotype in older animals (23, 24).”

    From Cardiac remodeling in obesity (2008) · cites this paper as [30]

  • In isovolumic ob/ob hearts, cardiac performance is similar at low work loads but significantly reduced at increased work loads.

    “In isovolumic ob/ob hearts, although cardiac performance was similar at low work loads, there was a significant reduction at increased work loads (30).”

    From Cardiac remodeling in obesity (2008) · cites this paper as [30]

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Authors
Boudina, S., Sena, S., O’Neill, B. T., Tathireddy, P., Young, M. E., & Abel, E. D.
Affiliations
  • Baylor College of Medicine (US)
  • From the Division of Endocrinology, Metabolism and Diabetes and Program in Human Molecular Biology and Genetics (S.B., S.S., B.T.O., P.T., E.D.A.), University of Utah School of Medicine, Salt Lake City, Utah, and USDA/ARS Children’s Nutrition Research Center and Department of Pediatrics (M.E.Y.), Baylor College of Medicine, Houston, Tex.
ORCID
Venue
Circulation
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2005-10-25
Volume
112
Issue
17
Pages
2686-2695
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
DOI
10.1161/circulationaha.105.554360
OpenAlex
W2160331251
Cited by
502
References
31
Citations by year
2026: 7 · 2025: 12 · 2024: 20 · 2023: 17 · 2022: 22 · 2021: 23 · 2020: 23 · 2019: 16 · 2018: 20 · 2017: 29 · 2016: 25 · 2015: 42 · 2014: 48 · 2013: 39 · 2012: 33
FWCI
6.15
Type
journal article
Language
en
Update notices
correction (2021-12-06)
Open access
closed
Locations
  • Circulation (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • American Diabetes Association
  • American Heart Association
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (R01HL073167, R01-HL-73167, UO1HL70525, U01HL070525)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK092065)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
Keywords
obesity, mitochondrial uncoupling, mitochondrial oxidative capacity, myocardial oxygen consumption, cardiac efficiency, cardiac energetics, ob/ob mice, palmitate, fatty acid metabolism, pyruvate dehydrogenase, mitochondrial respiration, ATP production, insulin resistance, type 2 diabetes, cardiac contractile function
MeSH terms
Adenosine Triphosphate, Animals, Energy Metabolism, Mice, Inbred C57BL, Mice, Obese, Mitochondria, Heart, Myocardium, Obesity, Oxidative Phosphorylation, Oxygen Consumption, Mice

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