Mitochondrial dysfunction in white adipose tissue

Abstract

Although mitochondria in brown adipose tissue and their role in non-shivering thermogenesis have been widely studied, we have only a limited understanding of the relevance of mitochondria in white adipose tissue (WAT) for cellular homeostasis of the adipocyte and their impact upon systemic energy homeostasis. A better understanding of the regulatory role that white adipocyte mitochondria play in the regulation of whole-body physiology becomes increasingly important. WAT mitochondrial biogenesis can effectively be induced pharmacologically using a number of agents, including PPARγ agonists. Through their ability to influence key biochemical processes central to the adipocyte, such as fatty acid (FA) esterification and lipogenesis, as well as their impact upon the production and release of key adipokines, mitochondria play a crucial role in determining systemic insulin sensitivity.

Figure 1. Proposed Pathways of Mitochondrial Dysfunction in the White Adipocyte

Metabolic challenges such as excess nutrient-intake that promote high FFAs concentrations and hyperglycemia, in addition to aging and ceramide formation, all increase mitochondrial ROS production to cause adipocyte mitochondrial dysfunction. Consequently, compromised mitochondrial function reduces mitochondrial biogenesis and mitochondrial DNA (mtDNA) content and decreases the rate of β-oxidation. As such, major adipocyte pathways are altered, such as adipogenesis, lipolysis, fatty acid esterification and adipocyte-derived adiponectin production; collectively, this promotes changes in insulin sensitivity. Improvements of mitochondrial function through therapeutic strategies, such as TZDs or antioxidant treatment, exercise and/or calorie restriction can restore insulin action, which leads to normalize cellular homeostasis.