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Review
. 2016 Aug 23;17(9):1379.
doi: 10.3390/ijms17091379.

Micronutrient Antioxidants and Nonalcoholic Fatty Liver Disease

Guanliang Chen  1 , Yinhua Ni  2 , Naoto Nagata  3 , Liang Xu  4 , Tsuguhito Ota  5
Affiliations
Review

Micronutrient Antioxidants and Nonalcoholic Fatty Liver Disease

Guanliang Chen et al. Int J Mol Sci. .

Abstract

Nonalcoholic fatty liver disease (NAFLD) is one of the most important chronic liver diseases worldwide and has garnered increasing attention in recent decades. NAFLD is characterized by a wide range of liver changes, from simple steatosis to nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. The blurred pathogenesis of NAFLD is very complicated and involves lipid accumulation, insulin resistance, inflammation, and fibrogenesis. NAFLD is closely associated with complications such as obesity, diabetes, steatohepatitis, and liver fibrosis. During the progression of NAFLD, reactive oxygen species (ROS) are activated and induce oxidative stress. Recent attempts at establishing effective NAFLD therapy have identified potential micronutrient antioxidants that may reduce the accumulation of ROS and finally ameliorate the disease. In this review, we present the molecular mechanisms involved in the pathogenesis of NAFLD and introduce some dietary antioxidants that may be used to prevent or cure NAFLD, such as vitamin D, E, and astaxanthin.

Keywords: antioxidants; astaxanthin; fibrosis; inflammation; insulin resistance; nonalcoholic fatty liver disease (NAFLD); nonalcoholic steatohepatitis (NASH); vitamin D; vitamin E.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Hypothetic mechanism of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) progression. Excessive intake of excess calories and fat results in accumulation of triglycerides, total cholesterol, and free fatty acids, inducing hepatic steatosis. The overload of liver lipids enhances lipid peroxidation, which induces the production of reactive oxygen species and steatohepatitis. Hepatic inflammation activates the mitogen-activated protein kinase pathway and nuclear factor-κB, resulting in insulin resistance. Insulin resistance also promotes de novo lipogenesis, forcing the healthy liver to develop NASH. The inflammation also recruits Kupffer cells and polarizes M1 macrophages, activating hepatic stellate cells and finally leading to liver fibrosis. TG, triglycerides; TC, total cholesterol; FFA, free fatty acids; MAPK, mitogen-activated protein kinase; NF-κB, nuclear factor-κB.
Figure 2
Figure 2
A brief comparison of NAFLD/NASH prevention and therapy between astaxanthin and vitamin E. First, astaxanthin is more effective than vitamin E in improving steatosis by suppressing lipid accumulation. Second, astaxanthin is superior to vitamin E with respect to suppressing the MAPK pathway and NF-κB activation and induces a strong shift of M2 macrophage polarization, which ultimately reverses hepatic steatosis, inflammation, and insulin resistance. Most importantly, as a result of M1/M2 transformation, astaxanthin can reduce hepatic stellate cell (HSC) activation and ameliorate hepatic fibrosis. Black arrow: ↑: induction, ↓: inhibition, →: no change; Red arrow: ↓: inhibition compared with vitamin E, ↑↑/↓↓: more significant induction/inhibition effect compared with vitamin E.
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