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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Category: Review Series

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 1

Inflammation in skeletal muscle in obesity.

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Inflammation in skeletal muscle in obesity. (A) In lean conditions, few ...
(A) In lean conditions, few immune cells with resting or antiinflammatory phenotypes reside in skeletal muscle. (B) As obesity develops and progresses along with expansion of visceral and subcutaneous AT, adipose depots expand between muscle fibers or surrounding muscle, so-called IMAT/PMAT. In obesity, immune cells including macrophages and T cells infiltrate into IMAT/PMAT and polarize into proinflammatory phenotypes, leading to increased inflammation in skeletal muscle. At the same time, myocytes may become inflamed and express proinflammatory cytokines and chemokines. (C) Chemokines and cytokines secreted by myocytes, adipocytes, and immune cells, along with FFAs that are transferred into skeletal muscle and ANG II produced within skeletal muscle, may themselves further accelerate immune cell recruitment and activation and myocyte inflammation, forming a feed-forward loop of inflammation in skeletal muscle.