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. 2020;1(4):160-168.

Improving Obesity and Insulin Resistance by Targeting Skeletal Muscle MKP-1

Anton M Bennett  1   2   3 , Ahmed Lawan  4
Affiliations

Improving Obesity and Insulin Resistance by Targeting Skeletal Muscle MKP-1

Anton M Bennett et al. J Cell Signal. 2020.

Abstract

Obesity has reached a global epidemic and it predisposes to the development of insulin resistance, type 2 diabetes and related metabolic diseases. Current interventions against obesity and/or type 2 diabetes such as calorie restriction, exercise, genetic manipulations or established pharmacological treatments have not been successful for many patients with obesity and/or type 2 diabetes. There is an urgent need for new strategies to treat insulin resistance, T2D and obesity. Increased activity of stress-responsive pathways has been linked to the pathogenesis of insulin resistance in obesity. In this commentary, we argue that chronic upregulation of MKP-1 in skeletal muscle is part of a stress response that contributes to the development of insulin resistance, T2D and obesity. Therefore, inhibition of MKP-1 in skeletal muscle is a potential strategy for the treatment of T2D and obesity. We highlight therapeutic strategies for potential targeting of MKP-1 in skeletal muscle for the treatment of metabolic diseases as well as other diseases of skeletal muscle.

Keywords: Insulin resistance; MAP kinase; MAP kinase phosphatase; Obesity.

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Conflict of interest statement

Conflict of Interest No potential conflicts of interest relevant to this article were reported.

Figures

Figure 1:
Figure 1:
Model for MKP-1 regulation of MAPK pathway in obese skeletal muscle. MKP-1 regulate the activities of p38 MAPK/JNK pathway. In obesity, MKP-1 is upregulated, which inhibit p38 MAPK thereby impairing PGC1a activity leading to decreased Mitochondrial function and reduced energy expenditure. Overexpression of MKP-1 also leads to development of insulin resistance by controlling the activation of p38 MAPK/JNK through the miR-21/PTEN/Akt pathway.
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