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Journal of Molecular Medicine

, Volume 88, Issue 10, pp 993–1001 | Cite as

Mitochondrial biogenesis in the metabolic syndrome and cardiovascular disease

  • Jun Ren
  • Lakshmi Pulakat
  • Adam Whaley-Connell
  • James R. SowersEmail author
Review

Abstract

The metabolic syndrome is a constellation of metabolic disorders including obesity, hypertension, and insulin resistance, components which are risk factors for the development of diabetes, hypertension, cardiovascular, and renal disease. Pathophysiological abnormalities that contribute to the development of the metabolic syndrome include impaired mitochondrial oxidative phosphorylation and mitochondrial biogenesis, dampened insulin metabolic signaling, endothelial dysfunction, and associated myocardial functional abnormalities. Recent evidence suggests that impaired myocardial mitochondrial biogenesis, fatty acid metabolism, and antioxidant defense mechanisms lead to diminished cardiac substrate flexibility, decreased cardiac energetic efficiency, and diastolic dysfunction. In addition, enhanced activation of the renin–angiotensin–aldosterone system and associated increases in oxidative stress can lead to mitochondrial apoptosis and degradation, altered bioenergetics, and accumulation of lipids in the heart. In addition to impairments in metabolic signaling and oxidative stress, genetic and environmental factors, aging, and hyperglycemia all contribute to reduced mitochondrial biogenesis and mitochondrial dysfunction. These mitochondrial abnormalities can predispose a metabolic cardiomyopathy characterized by diastolic dysfunction. Mitochondrial dysfunction and resulting lipid accumulation in skeletal muscle, liver, and pancreas also impede insulin metabolic signaling and glucose metabolism, ultimately leading to a further increase in mitochondrial dysfunction. Interventions to improve mitochondrial function have been shown to correct insulin metabolic signaling and other metabolic and cardiovascular abnormalities. This review explores mechanisms of mitochondrial dysfunction with a focus on impaired oxidative phosphorylation and mitochondrial biogenesis in the pathophysiology of metabolic heart disease.

Keywords

Metabolic impairment Oxidative phosphorylation Mitochondrial biogenesis 

Notes

Acknowledgements

Research included in this review is supported by NIH R01HL073101, VA Merit (JRS), and CDA-2 Dept of Veterans Affairs (AWC). The authors thank Brenda Hunter for her assistance in preparing this manuscript.

Conflict of interest statement

The authors declare no conflict of interests related to this study.

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Jun Ren
    • 1
  • Lakshmi Pulakat
    • 2
  • Adam Whaley-Connell
    • 2
  • James R. Sowers
    • 2
    • 3
    Email author
  1. 1.Center for Cardiovascular Research and Alternative MedicineUniversity of Wyoming College of Health SciencesLaramieUSA
  2. 2.Diabetes and Cardiovascular CenterUniversity of Missouri School of Medicine, VA Medical CenterColumbiaUSA
  3. 3.D109 HSC Diabetes CenterColumbiaUSA

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