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Skeletal muscle glucose metabolism and inflammation in the development of the metabolic syndrome

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Abstract

Insulin resistance and metabolic dysfunction in skeletal muscle play a major role in the development of the metabolic syndrome and type 2 diabetes. Numerous mechanisms have been proposed to explain the pathophysiology of obesity-linked metabolic dysfunction and this review will focus on the contributing role of adiponectin and inflammation. The beneficial effects of adiponectin on both insulin action and inflammation are now well documented and will be reviewed. More recent work provided new insights into adiponectin signaling mechanisms. The development of strategies to mimic adiponectin action holds promise that adiponectin-based compounds may translate into effective therapeutic applications. We will also discussed the novel role of long chain ω-3 PUFA-derived resolution mediators, which in addition to resolving inflammation, can also exert glucoregulatory effects in models of obesity and insulin resistance. We will focus on one resolution mediator, protectin DX (PDX), which was recently shown to act as a muscle interleukin-6 secretagogue. PDX and its isomer PD1 also enhance adiponectin expression and action. Ultimately, it is via a better understanding the molecular mechanisms of action via which inflammation, insulin resistance and metabolic dysfunction occur in skeletal muscle, and also how they crosstalk with each other, that we can generate new and improved therapies for obesity-linked metabolic complications.

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Acknowledgments

Related work in the authors laboratories is supported by operating grants from Canadian Diabetes Association (AM & GS), Heart & Stroke Foundation of Canada (GS), Canadian Institutes of Health Research (AM & GS). GS also acknowledges support via a Career Investigator Award from Heart & Stroke Fundation Ontario. AM was supported by a CIHR/Pfizer Research Chair in the pathogenesis of insulin resistance and cardiovascular diseases.

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Authors and Affiliations

  1. Department of Medicine, Faculty of Medicine and Heart and Lung Institute, Laval University, Québec, QC, Canada

    André Marette

  2. Department of Biology, York University, Toronto, ON, M3J 1P3, Canada

    Ying Liu & Gary Sweeney

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Marette, A., Liu, Y. & Sweeney, G. Skeletal muscle glucose metabolism and inflammation in the development of the metabolic syndrome. Rev Endocr Metab Disord 15, 299–305 (2014). https://doi.org/10.1007/s11154-014-9296-6

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