scholarly journals Dietary Flaxseed Oil Prevents Western-Type Diet-Induced Nonalcoholic Fatty Liver Disease in Apolipoprotein-E Knockout Mice

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Hao Han ◽  
Fubin Qiu ◽  
Haifeng Zhao ◽  
Haiying Tang ◽  
Xiuhua Li ◽  
...  

The prevalence of nonalcoholic fatty liver disease (NAFLD) has dramatically increased globally during recent decades. Intake of n-3 polyunsaturated fatty acids (PUFAs), mainly eicosapentaenoic acid (EPA, C20:5n-3) and docosahexaenoic acid (DHA, C22:6n-3), is believed to be beneficial to the development of NAFLD. However, little information is available with regard to the effect of flaxseed oil rich in α-linolenic acid (ALA, C18:3n-3), a plant-derived n-3 PUFA, in improving NAFLD. This study was to gain the effect of flaxseed oil on NAFLD and further investigate the underlying mechanisms. Apolipoprotein-E knockout (apoE-KO) mice were given a normal chow diet, a western-type high-fat and high-cholesterol diet (WTD), or a WTD diet containing 10% flaxseed oil (WTD + FO) for 12 weeks. Our data showed that consumption of flaxseed oil significantly improved WTD-induced NAFLD, as well as ameliorated impaired lipid homeostasis, attenuated oxidative stress, and inhibited inflammation. These data were associated with the modification effects on expression levels of genes involved in de novo fat synthesis (SREBP-1c, ACC), triacylglycerol catabolism (PPARα, CPT1A, and ACOX1), inflammation (NF-κB, IL-6, TNF-α, and MCP-1), and oxidative stress (ROS, MDA, GSH, and SOD).

Metabolites ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 55
Author(s):  
Tingyi Du ◽  
Qin Fang ◽  
Zhihao Zhang ◽  
Chuanmeng Zhu ◽  
Renfan Xu ◽  
...  

Aim: Lentinan (LNT), a type of polysaccharide derived from Lentinus edodes, has manifested protective effects during liver injury and hepatocellular carcinoma, but little is known about its effects on nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate whether LNT can affect the progression of NAFLD and the associated mechanisms. Methods: C57BL/6J mice were fed a normal chow diet or a high-fat diet (HFD) with or without LNT (6 mg/kg/d). AML12 cells were exposed to 200 μM palmitate acid (PA) with or without LNT (5 μg/mL). Results: After 21 wk of the high-fat diet, LNT significantly decreased plasma triglyceride levels and liver lipid accumulation, reduced excessive reactive oxygen species production, and subsequently attenuated hepatic apoptosis in NAFLD mice. These effects were associated with increased PPARα levels, a decreased Bax/Bcl-2 ratio, and enhancement of the antioxidant defense system in vivo. Similar effects were also observed in cultured cells. More importantly, these protective effects of LNT on palmitate acid-treated AML12 cells were almost abolished by PPARα knockdown. Conclusion: In conclusion, this study demonstrates that LNT may ameliorate hepatic steatosis and decrease oxidative stress and apoptosis by activating the PPARα pathway and is a potential drug target for NAFLD.


2018 ◽  
Vol 46 (06) ◽  
pp. 1315-1332 ◽  
Author(s):  
Ui-Jin Bae ◽  
Eun-Ock Park ◽  
John Park ◽  
Su-Jin Jung ◽  
Hyeonmi Ham ◽  
...  

Nonalcoholic steatohepatitis (NASH) arises from nonalcoholic fatty liver disease (NAFLD) as a consequence of oxidative stress. Gynostemma pentaphyllum extract (GPE) is proven to be beneficial for patients suffering from NAFLD. However, the precise mechanism by which GPE confers these benefits remains largely unknown. The purpose of this study was to investigate the underlying mechanism and to determine whether supplementation with the newly discovered GPE gypenoside UL4 mitigates NASH progression. Male c57BL/6 mice were fed a normal chow diet, a methionine choline-deficient (MCD) diet, or an MCD diet supplemented with various doses of UL4-rich GPE for eight weeks. GPE supplementation suppressed oxidative stress induced by the MCD diet by increasing levels of sirtuin 6 and phase 2 anti-oxidant enzymes in mouse liver and HepG2 cells. Additionally, GPE supplementation prevented diet-induced hepatic fat accumulation, hepatocellular injury, inflammation, and fibrosis in mice fed the MCD diet. These results indicate the possible therapeutic potential of dietary supplementation of UL4-rich GPE in preventing the development of fatty liver and its progression to NASH.


2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Po-Jung Wu ◽  
Jin-Bor Chen ◽  
Wen-Chin Lee ◽  
Hwee-Yeong Ng ◽  
Shu-Ching Lien ◽  
...  

Introduction. Nonalcoholic fatty liver disease (NAFLD) is becoming more common around the world and it may progress to cirrhosis and liver failure, increasing mortality risk. In hemodialysis (HD) patients, NAFLD may be a novel risk factor for their high cardiovascular mortality. Heightened oxidative stress is highly prevalent in HD patients. However, the relationship between oxidative stress and NAFLD in HD patients is not well defined.Methods. We studied seventy-one stable nondiabetic HD patients. Nineteen patients had the diagnosis of NAFLD by ultrasonography. Blood levels of oxidative stress markers were measured in each patient, including thiobarbituric acid reactive substances (TBARS), free thiols, superoxide dismutase (SOD) activities, and glutathione peroxidase (GPx) activity. The copy numbers of mitochondrial DNA (mtDNA) in peripheral leukocytes were also determined. Demographic, biochemistry, and hemogram data were recorded. The two groups of patients were compared in order to determine the factors associated with NAFLD in HD patients.Findings. Compared to those without NAFLD, nondiabetic HD patients with NAFLD had significantly higher mtDNA copy number and GPx levels. The two groups did not differ significantly in dialysis adequacy, hemoglobin, serum calcium, phosphorus, albumin, liver function tests, or lipid profiles. Regression analysis confirmed mtDNA copy numbers and GPx levels as two independent factors associated with NAFLD. Compared to those with polysulfone, patients dialyzed with cellulose membrane have significantly higher levels of TBARS. However, patients with or without NAFLD did not differ in their use of either dialysis membrane.Discussion. Oxidative stress (represented by antioxidant defense, GPx) and mitochondrial DNA copy numbers are independently associated with fatty liver disease in nondiabetic HD patients. The diagnostic and therapeutic implications of this key observation warrant further exploration.


2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Maria Luíza R. P. Lima ◽  
Laura H. R. Leite ◽  
Carolina R. Gioda ◽  
Fabíola O. P. Leme ◽  
Claudia A. Couto ◽  
...  

The pathogenesis of nonalcoholic fatty liver disease (NAFLD) is not fully understood, and experimental models are an alternative to study this issue. We investigated the effects of a simple carbohydrate-rich diet on the development of obesity-related NAFLD and the impact of physical training on the metabolic abnormalities associated with this disorder. Sixty Wistar rats were randomly separated into experimental and control groups, which were fed with sucrose-enriched (18% simple carbohydrates) and standard diet, respectively. At the end of each experimental period (5, 10, 20, and 30 weeks), 6 animals from each group were sacrificed for blood tests and liver histology and immunohistochemistry. From weeks 25 to 30, 6 animals from each group underwent physical training. The experimental group animals developed obesity and NAFLD, characterized histopathologically by steatosis and hepatocellular ballooning, clinically by increased thoracic circumference and body mass index associated with hyperleptinemia, and metabolically by hyperglycemia, hyperinsulinemia, hypertriglyceridemia, increased levels of very low-density lipoprotein- (VLDL-) cholesterol, depletion of the antioxidants liver enzymes superoxide dismutase and catalase, and increased hepatic levels of malondialdehyde, an oxidative stress marker. Rats that underwent physical training showed increased high-density lipoprotein- (HDL-) cholesterol levels. In conclusion, a sucrose-rich diet induced obesity, insulin resistance, oxidative stress, and NAFLD in rats.


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