A High-Fat, High-Fructose Diet Induces Antioxidant Imbalance and Increases the Risk and Progression of Nonalcoholic Fatty Liver Disease in Mice.

Kanokwan Jarukamjorn,Nattharat Jearapong,Charinya Pimson,Waranya Chatuphonprasert

doi:10.1155/2016/5029414

Kanokwan Jarukamjorn, Nattharat Jearapong + Show 2 more

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https://doi.org/10.1155/2016/5029414

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Journal: Scientifica	Publication Date: Jan 1, 2016
Citations: 86	License type: CC BY 4.0

Affiliation: Khon Kaen University, Mahasarakham University

Abstract

Excessive fat liver is an important manifestation of nonalcoholic fatty liver disease (NAFLD), associated with obesity, insulin resistance, and oxidative stress. In the present study, the effects of a high-fat, high-fructose diet (HFFD) on mRNA levels and activities of the antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), were determined in mouse livers and brains. The histomorphology of the livers was examined and the state of nonenzymatic reducing system was evaluated by measuring the glutathione system and the lipid peroxidation. Histopathology of the liver showed that fat accumulation and inflammation depended on the period of the HFFD-consumption. The levels of mRNA and enzymatic activities of SOD, CAT, and GPx were raised, followed by the increases in malondialdehyde levels in livers and brains of the HFFD mice. The oxidized GSSG content was increased while the total GSH and the reduced GSH were decreased, resulting in the increase in the GSH/GSSG ratio in both livers and brains of the HFFD mice. These observations suggested that liver damage and oxidative stress in the significant organs were generated by continuous HFFD-consumption. Imbalance of antioxidant condition induced by long-term HFFD-consumption might increase the risk and progression of NAFLD.

Highlights

Nonalcoholic fatty liver disease (NAFLD) is a condition in which excessive fat accumulates in the liver of a patient who drinks little or no alcohol
Cytokine production is altered in the nonalcoholic steatohepatitis (NASH) stage which is further characterized by lobular inflammation, hepatocyte ballooning, and fibrosis [5]
Bovine serum albumin (BSA), 5,5-dithiobis-(2-nitrobenzoic acid) (DTNB), glutathione reductase, oxidized glutathione (GSSG), reduced glutathione (GSH), nitrotetrazolium blue chloride (NBT), reduced β-nicotinamide adenine dinucleotide phosphate (NADPH), standard malondialdehyde (MDA), standard superoxide dismutase (SOD) from bovine erythrocytes, 4-vinylpyridine (4-VP), and xanthine oxidase were from Sigma Aldrich

Summary

Introduction

Nonalcoholic fatty liver disease (NAFLD) is a condition in which excessive fat accumulates in the liver of a patient who drinks little or no alcohol. The development of NAFLD is associated with obesity, insulin resistance (diabetes mellitus type 2), and hyperlipidemia [1] and is characterized by the accumulation of fatty acids, especially excess triglycerides, in hepatocytes [2]. Cytokine production is altered in the NASH stage which is further characterized by lobular inflammation, hepatocyte ballooning, and fibrosis [5]. Other factors, such as oxidative injury or oxidative stress, are required to shift from NASH to liver cirrhosis, before leading to hepatocellular carcinoma, in severe cases [6]. Increases in SOD and GPx activity and SOD, GPx, and CAT mRNA expression in the livers of rabbits fed a high-fat diet have indicated a significant role for the antioxidant system in NAFLD [8]

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