Modulation of Insulin Resistance and the Adipocyte-Skeletal Muscle Cell Cross-Talk by LCn-3PUFA.

Alexandre Pinel,Frédéric Capel,Jean-Paul Rigaudière,Chrystèle Jouve

doi:10.3390/ijms19092778

Abstract

The cross-talk between skeletal muscle and adipose tissue is involved in the development of insulin resistance (IR) in skeletal muscle, leading to the decrease in the anabolic effect of insulin. We investigated if the long chain polyunsaturated n-3 fatty acids (LCn-3PUFA), eicosapentaenoic and docosapentaenoic acids (EPA and DPA, respectively) could (1) regulate the development of IR in 3T3-L1 adipocytes and C2C12 muscle cells and (2) inhibit IR in muscle cells exposed to conditioned media (CM) from insulin-resistant adipocytes. Chronic insulin (CI) treatment of adipocytes and palmitic acid (PAL) exposure of myotubes were used to induce IR in the presence, or not, of LCn-3PUFA. EPA (50 µM) and DPA (10 µM) improved PAL-induced IR in myotubes, but had only a partial effect in adipocytes. CM from adipocytes exposed to CI induced IR in C2C12 myotubes. Although DPA increased the mRNA levels of genes involved in fatty acid (FA) beta-oxidation and insulin signaling in adipocytes, it was not sufficient to reduce the secretion of inflammatory cytokines and prevent the induction of IR in myotubes exposed to adipocyte’s CM. Treatment with DPA was able to increase the release of adiponectin by adipocytes into CM. In conclusion, DPA is able to protect myotubes from PAL-induced IR, but not from IR induced by CM from adipocytes.

Highlights

In 2060, the European population is expected to reach 517 million and one third of people will be more than 65 years old [1]
docosapentaenoic acid (DPA) relative abundance in PC was enhanced in adipocytes exposed to DPA compared to those treated with chronic insulin (CI) only (p = 0.013 vs. CI)
Several studies have previously demonstrated the beneficial effects of eicosapentaenoic acid (EPA) or DHA, two LCn-3PUFA on insulin resistance (IR) in skeletal muscle cells exposed to high concentrations of palmitic acid (PAL) [10,17,18]

Summary

Introduction

In 2060, the European population is expected to reach 517 million and one third of people will be more than 65 years old [1] This represents a significant public health challenge with a major economic cost, notably because of several associated chronic diseases. Variations in lean and fat masses have common pathophysiological mechanisms, including insulin-resistance (IR), a low-grade inflammation [2], and specific dysfunctions of adipose tissue and skeletal muscle metabolisms. These abnormalities are involved in the development of anabolic resistance of skeletal muscle cells and the progressive muscle atrophy observed during aging. The contribution of IL-6 and TNF-α production by muscle cells [4] to systemic inflammation is unclear but it was shown that chronically increased plasma levels of IL-6 and TNF-α could mediate insulin and anabolic resistance of skeletal muscle’s cells [5,6]

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Conclusion