Astaxanthin n-Octanoic Acid Diester Ameliorates Insulin Resistance and Modulates Gut Microbiota in High-Fat and High-Sucrose Diet-Fed Mice.

Yuan Gao,Qingjuan Tang,Shihan Yuan,Fang Liu,Yaoxian Chin,Changhu Xue,Jie Xu,Robert W Li,Lu Yang

doi:10.3390/ijms21062149

Abstract

Astaxanthin n-octanoic acid diester (AOD) is a type of astaxanthin connecting medium-chain fatty acids with a more stable structure. In this study, we examined the role of AOD in ameliorating insulin resistance (IR) induced by a high-fat and high-sucrose diet (HFD) as well as its effect on modulating gut microbiota in mice, with free astaxanthin (AST) as a comparison. Four groups of male C57BL/6J mice (6 weeks old; n = 10 per group) were fed with a normal control diet (NC), HFD orally administered with AOD, AST (50 mg/kg body weight), or vehicle for 8 weeks. AOD improved glucose tolerance, IR, systematic and intestinal inflammation, and intestinal integrity better than AST. Further, both AOD and AST modulated gut microbiota. A significantly higher abundance of Bacteroides and Coprococcus was found in AOD than in AST, and the predicted pathway of carbohydrate metabolism was significantly impacted by AOD. Overall, AOD may play a role in alleviating IR and inflammation with the modulating effect on microbiota in HFD-fed mice. Our findings could facilitate the development of AOD as a bioactive nutraceutical and more stable alternative to AST.

Highlights

Due to people’s preference for a high-fat and high-sucrose diet (HFD), chronic metabolic diseases such as insulin resistance (IR), weight gain, and dyslipidemia are becoming increasingly common [1]
The administration of AOD and AST significantly improved glucose tolerance compared to the HFD group (Figure 2A)
Compared to the mice fed with a normal diet, HFD significantly increased the area under the curve (AUC) in the oral glucose tolerance test (OGTT), whereas mice treated with AOD and AST had a reduced AUC by approximately 13% (p < 0.05; Figure 2B)

Summary

Introduction

Due to people’s preference for a high-fat and high-sucrose diet (HFD), chronic metabolic diseases such as insulin resistance (IR), weight gain, and dyslipidemia are becoming increasingly common [1]. As HFD impairs the tight junction of intestinal epithelial cells and increases intestinal permeability [5], endotoxin from microbiota transfer from the bowel lumen into the bloodstream through the impaired intestinal barrier, thereby inducing obesity and leading to IR [3]. These metabolic disorders are associated with a state of chronic, low-grade systemic inflammation, which is caused by the activation of immune cells such as macrophages and T lymphocytes, as well as the production of proinflammatory cytokines such as tumor necrosis factor (TNF), interleukin 1β (IL-1β), and interferon-γ (IFN-γ) [6,7,8,9]

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Conclusion