Protective Effects of Sesamol against Liver Oxidative Stress and Inflammation in High-Fat Diet-Induced Hepatic Steatosis

Chronic high-fat diet (HFD) is associated with the onset and progression of hepatic steatosis, and oxidative stress is highly involved in this process. The potential role of sesamol (SEM) against oxidative stress and inflammation at the transcriptional level in a mice model of hepatic steatosis is not known. In this study, we aimed to investigate the scavenging effects of SEM towards reactive oxygen generated by lipid accumulation in the liver of obese mice and to explore the mechanisms of protection. Markers of oxidative stress, vital enzymes involved in stimulating oxidative stress or inflammation, and nuclear transcription of Nrf2 were examined. Our results showed that SEM significantly inhibited the activity of the HFD-induced hepatic enzymes CYP2E1 and NOX2, associated with oxidative stress generation. Additionally, SEM reversed HFD-induced activation of NF-κB, a redox-sensitive transcription factor, and attenuated the expression of hepatic TNF-α, a proinflammatory molecule. Moreover, SEM enhanced HFD-induced hepatic Nrf2 nuclear transcription and increased the levels of its downstream target genes Ho1 and Nqo1, which indicated antiinflammation and antioxidant properties. Our study suggests that chronic HFD led to hepatic steatosis, while SEM exhibited protective effects on the liver by counteracting the oxidative stress and inflammation induced by HFD. The underlying mechanism might involve multiple pathways at the transcriptional level; the antioxidant defense mechanism was in partly mediated by the upregulation of Nrf2.

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Açaí (Euterpe oleracea Mart.) seed extract protects against hepatic steatosis and fibrosis in high-fat diet-fed mice: Role of local renin-angiotensin system, oxidative stress and inflammation

Journal of Functional Foods ◽

10.1016/j.jff.2019.103726 ◽

2020 ◽

Vol 65 ◽

pp. 103726 ◽

Cited By ~ 4

Author(s):

Matheus Henrique Romão ◽

Graziele Freitas de Bem ◽

Izabelle Barcellos Santos ◽

Ricardo de Andrade Soares ◽

Dayane Teixeira Ognibene ◽

...

Keyword(s):

Oxidative Stress ◽

Hepatic Steatosis ◽

High Fat Diet ◽

Renin Angiotensin System ◽

Seed Extract ◽

Euterpe Oleracea ◽

High Fat ◽

Angiotensin System ◽

Euterpe Oleracea Mart

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Antioxidant Properties of Fucoidan Alleviate Acceleration and Exacerbation of Hippocampal Neuronal Death Following Transient Global Cerebral Ischemia in High-Fat Diet-Induced Obese Gerbils

International Journal of Molecular Sciences ◽

10.3390/ijms20030554 ◽

2019 ◽

Vol 20 (3) ◽

pp. 554 ◽

Cited By ~ 13

Author(s):

Ji Ahn ◽

Myoung Shin ◽

Dae Kim ◽

Hyunjung Kim ◽

Minah Song ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Antioxidant Enzymes ◽

Cerebral Ischemia ◽

Neuronal Death ◽

High Fat Diet ◽

Antioxidant Properties ◽

Global Cerebral Ischemia ◽

High Fat ◽

Transient Global Cerebral Ischemia

Fucoidan, a natural sulfated polysaccharide, displays various biological activities including antioxidant properties. We examined the neuroprotective effect of fucoidan against transient global cerebral ischemia (tGCI) in high-fat diet (HFD)-induced obese gerbils and its related mechanisms. Gerbils received HFD for 12 weeks and fucoidan (50 mg/kg) daily for the last 5 days during HFD exposure, and they were subjected to 5-min tGCI. Pyramidal cell death was observed only in the CA 1 area (CA1) of the hippocampus in non-obese gerbils 5 days after tGCI. However, in obese gerbils, pyramidal cell death in the CA1 and CA2/3 occurred at 2 days and 5 days, respectively, after tGCI. In the obese gerbils, oxidative stress indicators (dihydroethidium, 8-hydroxyguanine and 4-hydroxy-2-nonenal) were significantly enhanced and antioxidant enzymes (SOD1 and SOD2) were significantly reduced in pre- and post-ischemic phases compared to the non-obese gerbils. Fucoidan treatment attenuated acceleration and exacerbation of tGCI-induced neuronal death in the CA1–3, showing that oxidative stress was significantly reduced, and antioxidant enzymes were significantly increased in pre- and post-ischemic phases. These findings indicate that pretreated fucoidan can relieve the acceleration and exacerbation of ischemic brain injury in an obese state via the attenuation of obesity-induced severe oxidative damage.

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Neural Protective Effects of Millet and Millet Polyphenols on High-Fat Diet-Induced Oxidative Stress in the Brain

Plant Foods for Human Nutrition ◽

10.1007/s11130-020-00802-6 ◽

2020 ◽

Vol 75 (2) ◽

pp. 208-214 ◽

Cited By ~ 1

Author(s):

Sen Li ◽

Furong Xian ◽

Xiao Guan ◽

Kai Huang ◽

Wenwen Yu ◽

...

Keyword(s):

Oxidative Stress ◽

High Fat Diet ◽

Protective Effects ◽

High Fat ◽

The Brain

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Effect of Training Intensity on Hepatic Steatosis and Expression of miRNAs and Target Genes in a High-fat Diet-induced Mice

Exercise Science ◽

10.15857/ksep.2018.27.1.32 ◽

2018 ◽

Vol 27 (1) ◽

pp. 32-39

Author(s):

Jinkyung Cho ◽

Jinhwan Yoon ◽

Inho Park ◽

Hyunsik Kang

Keyword(s):

Hepatic Steatosis ◽

High Fat Diet ◽

Target Genes ◽

Training Intensity ◽

High Fat

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Melatonin protects against cardiac damage induced by a combination of high fat diet and isoproterenol exacerbated oxidative stress in male Wistar rats

Melatonin Research ◽

10.32794/mr11250009 ◽

2019 ◽

Vol 2 (1) ◽

pp. 9-31 ◽

Cited By ~ 1

Author(s):

Auroma Ghosh ◽

Gargi Bose ◽

Tiyasa Dey ◽

Palash Kumar Pal ◽

Sanatan Mishra ◽

...

Keyword(s):

Oxidative Stress ◽

Antioxidant Enzymes ◽

High Fat Diet ◽

Myocardial Damage ◽

Neutrophil Infiltration ◽

Protective Effects ◽

High Fat ◽

Cardiac Damage ◽

Male Wistar Rats ◽

Abnormal Mitochondria

In the current study, it was found that high fat diet (60% of total kCal) (H) or/and isoproterenol (I) exacerbated oxidative stress and caused myocardial damage. This was indicated by increased levels of LPO, PCO, abnormal mitochondria and altered activities of metabolic as well as antioxidant enzymes in myocardium of rats. Melatonin at different doses (10, 20 and 40 mg/kg) effectively protected against myocardial damage induced by H or/and I and preserved all of these altered parameters. Morphological analyses showed that combination of H and I treatment led to the extensive myofibril disintegration and neutrophil infiltration. Melatonin at the dose of 40 mg/kg almost completely prevented these pathological alterations. The mechanistical studies have uncovered that the protective effects of melatonin on the myocardial damage induced by H and I are attributed to its direct and indirect antioxidative capacity, i.e., it directly scavenges free radicals and also regulates the gene expression of antioxidant enzymes. Collectively, based on the evidences gathered from the current study, it will not be unwise to suggest that melatonin can serve as an ideal therapeutic agent for those cardiovascular diseases caused by oxidative stress.

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Variable penetrance of metabolic phenotypes and development of high-fat diet-induced adiposity in NEIL1-deficient mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00387.2010 ◽

2011 ◽

Vol 300 (4) ◽

pp. E724-E734 ◽

Cited By ~ 27

Author(s):

Harini Sampath ◽

Ayesha K. Batra ◽

Vladimir Vartanian ◽

J. Russ Carmical ◽

Deborah Prusak ◽

...

Keyword(s):

Oxidative Stress ◽

Mitochondrial Dna ◽

Oxygen Consumption ◽

Hepatic Steatosis ◽

High Fat Diet ◽

Late Onset ◽

Excision Repair ◽

High Fat ◽

Hepatic Expression ◽

Base Excision

Exposure to chronic and acute oxidative stress is correlated with many human diseases, including, but not limited to, cancer, heart disease, diabetes, and obesity. In addition to cellular lipids and proteins, cellular oxidative stress can result in damage to DNA bases, especially in mitochondrial DNA. We previously described the development of spontaneous late-onset obesity, hepatic steatosis, hyperinsulinemia, and hyperleptinemia in mice that are deficient in the DNA glycosylase nei-like 1 (NEIL1), which initiates base excision repair of several oxidatively damaged bases. In the current study, we report that exposure to a chronic oxidative stress in the form of a high-fat diet greatly accelerates the development of obesity in neil1−/− mice. Following a 5-wk high-fat diet challenge, neil1−/− mice gained significantly more body weight than neil1+/+ littermates and had increased body fat accumulation and moderate to severe hepatic steatosis. Analysis of oxygen consumption by indirect calorimetry indicated a modest reduction in total oxygen consumption in neil1−/− mice that was abolished upon correction for lean body mass. Additionally, hepatic expression of several inflammatory genes was significantly upregulated in neil1−/− mice following high-fat diet challenge compared with chow-fed or neil1+/+ counterparts. A long-term high-fat diet also induced glucose intolerance as well as a significant reduction in mitochondrial DNA and protein content in neil1−/− mice. Collectively, these data indicate that NEIL1 deficiency results in an increased susceptibility to obesity and related complications potentially by lowering the threshold for tolerance of cellular oxidative stress in neil1−/− mice.

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ERRATUM FOR “α7-Nicotinic Acetylcholine Receptor Agonist Ameliorates Nicotine Plus High-Fat Diet–Induced Hepatic Steatosis in Male Mice by Inhibiting Oxidative Stress and Stimulating AMPK Signaling”

Endocrinology ◽

10.1210/en.2018-00126 ◽

2018 ◽

Vol 159 (3) ◽

pp. 1416-1416

Keyword(s):

Oxidative Stress ◽

Hepatic Steatosis ◽

Nicotinic Acetylcholine Receptor ◽

High Fat Diet ◽

Receptor Agonist ◽

Male Mice ◽

High Fat ◽

Α7 Nicotinic Acetylcholine Receptor ◽

Nicotinic Acetylcholine ◽

Ampk Signaling

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Lipoic Acid Prevents High-Fat Diet-Induced Hepatic Steatosis in Goto Kakizaki Rats by Reducing Oxidative Stress Through Nrf2 Activation

International Journal of Molecular Sciences ◽

10.3390/ijms19092706 ◽

2018 ◽

Vol 19 (9) ◽

pp. 2706 ◽

Cited By ~ 9

Author(s):

Cristina Sena ◽

Maria Cipriano ◽

Maria Botelho ◽

Raquel Seiça

Keyword(s):

Oxidative Stress ◽

Type 2 Diabetes ◽

Liver Function ◽

Hepatic Steatosis ◽

Lipoic Acid ◽

High Fat Diet ◽

Control Group ◽

High Fat ◽

Tnf Α

Prevention of hepatic fat accumulation may be an important approach for liver diseases due to the increased relevance of hepatic steatosis in this field. This study was conducted to investigate the effects of the antioxidant α-lipoic acid (α-LA) on hepatic steatosis, hepatocellular function, and oxidative stress in a model of type 2 diabetes fed with a high fat diet (HFD). Goto-Kakizaki rats were randomly divided into four groups. The first group received only a standard rat diet (control GK) including groups 2 (HFD), 3 (vehicle group), and 4 (α-LA group), which were given HFD, ad libitum during three months. Wistar rats are the non-diabetic control group. Carbohydrate and lipid metabolism, liver function, plasma and liver tissue malondialdehyde (MDA), liver GSH, tumor necrosis factor-α (TNF-α) and nuclear factor E2 (erythroid-derived 2)-related factor-2 (Nrf2) levels were assessed in the different groups. Liver function was assessed using quantitative hepatobiliary scintigraphy, serum aspartate, and alanine aminotransferases (AST, ALT), alkaline phosphatase, gamma-glutamyltranspeptidase, and bilirubin levels. Histopathologically steatosis and fibrosis were evaluated. Type 2 diabetic animals fed with HFD showed a marked hepatic steatosis and a diminished hepatic extraction fraction and both were fully prevented with α-LA. Plasma and liver tissue MDA and hepatic TNF-α levels were significantly higher in the HFD group when compared with the control group and significantly lower in the α-LA group. Systemic and hepatic cholesterol, triglycerides, and serum uric acid levels were higher in hyperlipidemic GK rats and fully prevented with α-LA. In addition, nuclear Nrf2 activity was significantly diminished in GK rats and significantly augmented after α-LA treatment. In conclusion, α-LA strikingly ameliorates steatosis in this animal model of diabetes fed with HFD by decrementing the inflammatory marker TNF-α and reducing oxidative stress. α-LA might be considered a useful therapeutic tool to prevent hepatic steatosis by incrementing antioxidant defense systems through Nrf2 and consequently decreasing oxidative stress and inflammation in type 2 diabetes.

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