Molecular insight and pharmacological approaches targeting mitochondrial dynamics in skeletal muscle during obesity

Abstract

Obesity-associated insulin resistance is the major characteristic of the early stage of metabolic syndrome. A decline in mitochondrial function plays a role in the development of insulin resistance in obesity and type 2 diabetes. Accumulating data reveal that mitochondrial dynamics, the balance between mitochondrial fusion and fission, are an important factor in the maintenance of mitochondrial function. Thus, the mechanisms underlying the regulation of mitochondrial dynamics in obesity deserve further investigation. This review describes an overview of mitochondrial fusion and fission machineries, and discusses the mechanistic and functional aspects of mitochondrial dynamics, with a focus on skeletal muscle in obesity. Finally, we discuss current pharmacological approaches of targeting mitochondrial dynamics. Elucidating the role of mitochondrial dynamics in skeletal muscle afflicted by obesity may provide not only important clues in understanding muscle insulin resistance, but also new therapeutic targets.

Keywords: insulin resistance; lipid accumulation; mitochondrial morphology; posttranslational modification; skeletal muscle.