Skeletal muscle inflammation and insulin resistance in obesity
Huaizhu Wu, Christie M. Ballantyne
Huaizhu Wu, Christie M. Ballantyne
Published January 3, 2017
Citation Information: J Clin Invest. 2017;127(1):43-54. https://doi.org/10.1172/JCI88880.
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Skeletal muscle inflammation and insulin resistance in obesity

Abstract

Obesity is associated with chronic inflammation, which contributes to insulin resistance and type 2 diabetes mellitus. Under normal conditions, skeletal muscle is responsible for the majority of insulin-stimulated whole-body glucose disposal; thus, dysregulation of skeletal muscle metabolism can strongly influence whole-body glucose homeostasis and insulin sensitivity. Increasing evidence suggests that inflammation occurs in skeletal muscle in obesity and is mainly manifested by increased immune cell infiltration and proinflammatory activation in intermyocellular and perimuscular adipose tissue. By secreting proinflammatory molecules, immune cells may induce myocyte inflammation, adversely regulate myocyte metabolism, and contribute to insulin resistance via paracrine effects. Increased influx of fatty acids and inflammatory molecules from other tissues, particularly visceral adipose tissue, can also induce muscle inflammation and negatively regulate myocyte metabolism, leading to insulin resistance.

Authors

Huaizhu Wu, Christie M. Ballantyne

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Figure 2

Inflammatory effects on myocytes in obesity.

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Inflammatory effects on myocytes in obesity. In obesity, increased infil...
In obesity, increased infiltration and activation of immune cells in skeletal muscle (mainly in IMAT/PMAT) and myocyte inflammation lead to increased secretion of proinflammatory cytokines, which negatively regulate myocyte metabolic functions through paracrine or autocrine effects. Inflammation in visceral AT, with increased secretion of inflammatory adipokines, may also adversely affect myocyte metabolic function through endocrine effects. In addition, inflammatory effects on adipocytes in visceral AT and IMAT/PMAT may accelerate FFA release and transfer into myocytes, resulting in myocyte inflammation and metabolic dysfunction. Furthermore, elevated levels of TGRLs, including diet/enterocyte-derived chylomicrons (CM) and liver-derived VLDL may undergo enhanced LPL-mediated triglyceride hydrolysis, increasing FA release and transfer into skeletal muscle (and AT) and contributing to myocyte inflammation and metabolic dysfunctions. Activation of the RAS in skeletal muscle with local production of ANG II and ANG 1–7 may also regulate myocyte inflammation and metabolic functions.