Abstract

Laminaria japonica (LJ) and Hizikia fusiforme (HF) are brown seaweeds known to have various health-promoting effects. In this study, we investigated the anti-diabetic effects and possible mechanism(s) of LJ and HF by using both in vitro and in vivo models. C2C12 myotubes, mouse-derived skeletal muscle cells, treated with LF or HF extracts were used for the in vitro model, and muscle tissues from C57BL/6N mice fed a high-fat diet supplemented with 5% LF or HF for 16 weeks were used for the in vivo model. Although both the LF and HF extracts significantly inhibited α-glucosidase activity in a dose-dependent manner, the HF extract had a superior α-glucosidase inhibition than the LF extract. In addition, glucose uptake was significantly increased by LJ- and HF-treated groups when compared to the control group. Phosphorylation of protein kinase B and AMP-activated protein kinase was induced by LJ and HF in both the vivo and in vitro skeletal muscle models. Furthermore, LJ and HF significantly decreased tumor necrosis factor-α whereas both extracts increased interleukin (IL)-6 and IL-10 production in lipopolysaccharide-stimulated C2C12 myotubes. Taken together, these findings imply that the brown seaweeds LJ and HF could be useful therapeutic agents to attenuate muscle insulin resistance due to diet-induced obesity and its associated inflammation.

Highlights

  • Obesity causes enlarged adipocytes along with the infiltration of immune cells to induce chronic low-grade systemic inflammation, which further increases the production of free fatty acids and the number of inflammatory cytokines in circulation [1]

  • We demonstrated that mice fed a high-fat diet (HFD, 60% calories from fat) supplemented with four types of brown seaweeds (Undaria pinnatifida (UP), Laminaria Japonica (LJ), Sargassum Fulvellum (SF), and Hizikia Fusiforme (HF)) for 16 weeks showed that only Laminaria japonica (LJ) supplementation improved insulin sensitivity when compared to mice fed an HFD only based on an insulin tolerance test [15]

  • It has been well-reported that obesity-induced chronic inflammation causes insulin resistance in muscle, liver, and adipose cells, which contribute a systemic insulin resistance as well as producing pro-inflammatory cytokines, such as TNF-α and IL-6, for a feed-forward mechanism [1]

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Summary

Introduction

Obesity causes enlarged adipocytes along with the infiltration of immune cells to induce chronic low-grade systemic inflammation, which further increases the production of free fatty acids and the number of inflammatory cytokines in circulation [1]. It has been more than two decades since the molecular pathways that link inflammation and insulin resistance have been demonstrated [2,3]. Insulin signaling to promote glucose uptake in skeletal muscle is initiated by activating phosphatidylinositol-3 kinase and Akt (Protein Kinase B) [5]. It is known that AMPK is activated by exercise and anti-diabetic drugs, such as metformin, as well as various phytochemicals [8]

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