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

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.

Rice Bran Oil Improves Insulin Resistance by Affecting the Expression of Antioxidants and Lipid‐Regulatory Genes

“…These results agree with Cavarape et al () who recorded downregulation in hepatic Cat and Sod1 expression in HFD‐fed rats. While disagree with the results of Jarukamjorn, Jearapong, Pimson, and Chatuphonprasert () who reported that the mRNA level and enzymatic activity of SOD, CAT, and GPx were increased in liver of mice fed on a high‐fat, HFD for 2–8 weeks. It was reported that transcription factors are sensitive to the changes in the redox state of the cell, so it may be modulated by fructose‐induced oxidative stress (Allen & Tresini, ).…”

Gold-quercetin nanoparticles prevent metabolic endotoxemia-induced kidney injury by regulating TLR4/NF-kB signaling and Nrf2 pathway in high fat diet fed mice

“…11,12 Of note, on one hand, biomechanical experiments and clinical observations have illustrated that long-term intake of HFD results in lipid accumulation and endotoxemia, which can cause increase in inflammatory cytokines in the serum and organs and inflammationrelated signaling activation, promoting the development of nonalcoholic fatty liver disease (NAFLD) and systemic disorder. 11,[13][14][15] On the other hand, HFD significantly increases the production of reactive oxygen species (ROS), which further release superoxide anion and cause oxidative stress in the kidney by stimulating podocyte injury. [15][16][17] Hence, antioxidant therapy may be involved in the pathological process of kidney injury.…”

“…11,[13][14][15] On the other hand, HFD significantly increases the production of reactive oxygen species (ROS), which further release superoxide anion and cause oxidative stress in the kidney by stimulating podocyte injury. [15][16][17] Hence, antioxidant therapy may be involved in the pathological process of kidney injury. Previous reports show that TLR4/ NF-kB and mitogen-activated protein kinase (MAPK) pathways are involved in cellular inflammation in response to oxidative stress.…”

Comparisons of cardioprotective efficacy between fibroblast growth factor 21 and dipeptidyl peptidase‐4 inhibitor in prediabetic rats

“…It is interesting that mitochondrial lipid accumulation is counted as a major cause of higher cardiac mitochondrial ROS production in HFD feeding models . A previous study has also demonstrated that HFD caused an imbalance between free radicals and antioxidants, with a subsequent increase in mitochondrial ROS levels. Bax protein expression is recruited to the mitochondrial membrane during mitochondrial stress which could be a cause of mitochondrial membrane depolarization .…”