Mitochondrial dysfunction in obesity

aDepartments of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Current opinion in endocrinology, diabetes, and obesity (Impact Factor: 3.37). 10/2010; 17(5):446-52. DOI: 10.1097/MED.0b013e32833c3026
Source: PubMed


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.
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.
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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Available from: Juan C Bournat, Nov 14, 2014
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    • "This newly discovered ''plasticity'' of adipocytes has intensified efforts to identify novel methods to treat obesity and insulin resistance by increasing browning and peripheral energy expenditure (Boss and Farmer, 2012; Cypess and Kahn, 2010). Mitochondrial dysfunction has been shown to be associated with the development of obesity and insulin resistance (Bournat and Brown, 2010; Patti and Corvera, 2010). The peroxisome proliferator-activated receptor g coactivator-1a (PGC-1a) is a central transcriptional regulator of mitochondrial and peroxisomal remodeling and biogenesis (Wu et al., 1999; Bagattin et al., 2010). "
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    • "Mitochondrial structure and functions are constantly adjusted to maintain cellular metabolic homeostasis. Defects in mitochondrial functions have been associated to different pathologies, including obesity, type-2 diabetes, and neurodegenerative diseases [1–4]. In peripheral tissues, insulin-resistance is associated with mitochondrial dysfunctions in myocytes, hepatocytes, adipocytes, and islets β-cells [2,5]. "
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    • "Brown adipose tissue has a high mitochondrial density [8] and MnSOD mRNA was about 10-fold more abundant when compared to white fat depots with similar MnSOD mRNA levels (Fig. 1A–D). MnSOD protein was equally abundant in subcutaneous and visceral fat of mice kept on a SD (Fig. 3A, Table S2, 2.). "
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