Mitochondrial dysfunction in obesity - PubMed (original) (raw)

Review

Mitochondrial dysfunction in obesity

Juan C Bournat et al. Curr Opin Endocrinol Diabetes Obes. 2010 Oct.

Abstract

Purpose of review: The review highlights recent findings regarding the functions of mitochondria in adipocytes, providing an understanding of their central roles in regulating substrate metabolism, energy expenditure, disposal of reactive oxygen species (ROS), and in the pathophysiology of obesity and insulin resistance, as well as roles in the mechanisms that affect adipogenesis and mature adipocyte function.

Recent findings: Nutrient excess leads to mitochondrial dysfunction, which in turn leads to obesity-related pathologies, in part due to the harmful effects of ROS. The recent recognition of 'ectopic' brown adipose in humans suggests that this tissue may play an underappreciated role in the control of energy expenditure. Transcription factors, PGC-1alpha and PRDM16, which regulate brown adipogenesis, and members of the TGF-beta superfamily that modulate this process may be important new targets for antiobesity drugs.

Summary: Mitochondria play central roles in ATP production, energy expenditure, and disposal of ROS. Excessive energy substrates lead to mitochondrial dysfunction with consequential effects on lipid and glucose metabolism. Adipocytes help to maintain the appropriate balance between energy storage and expenditure and maintaining this balance requires normal mitochondrial function. Many adipokines, including members of the TGF-beta superfamily, and transcriptional coactivators, PGC-1alpha and PRDM16, are important regulators of this process.

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References

    1. Bogacka I, Xie H, Bray GA, et al. Pioglitazone induces mitochondrial biogenesis in human subcutaneous adipose tissue in vivo. Diabetes. 2005;54:1392–1399. - PubMed
    1. Gao CL, Zhu C, Zhao YP, et al. Mitochondrial dysfunction is induced by high levels of glucose and free fatty acids in 3T3-L1 adipocytes. Mol Cell Endocrinol. 2010;320:25–33. The paper shows that high levels of glucose and NEFAs, two well-known indicators of insulin resistance an T2D, result in mitochondrial dysfunction in 3T3-L1 pre-adipocytes.
    1. Koh EH, Park JY, Park HS, et al. Essential role of mitochondrial function in adiponectin synthesis in adipocytes. Diabetes. 2007;56:2973–2981. - PubMed
    1. Sutherland LN, Capozzi LC, Turchinsky NJ, et al. Time course of high-fat diet-induced reductions in adipose tissue mitochondrial proteins: potential mechanisms and the relationship to glucose intolerance. Am J Physiol Endocrinol Metab. 2008;295:E1076–E1083. - PubMed
    1. Feldmann HM, Golozoubova V, Cannon B, et al. UCP1 ablation induces obesity and abolishes diet-induced thermogenesis in mice exempt from thermal stress by living at thermoneutrality. Cell Metab. 2009;9:203–209. This is the first paper to demonstrate that UCP1 ablation induces obesity, but only under thermoneutral conditions. This is in contrast to previous reports indicating that UCP1 knockout mice did not develop obesity; however, the effects of thermal environment had not been carefully considered.

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