Abstract
Oxidative stress and inflammation contribute to hypertriglyceridemia‐induced nonalcoholic fatty liver disease (NAFLD). Cholesterol‐enriched diets increase the risk of NAFLD. Lycium ruthenium Murr. (LRM) contains water‐soluble antioxidant proanthocyanidins. Whether Lycium ruthenium Murr. improves NAFLD remains elusive. In this study, we established a model of NAFLD‐induced by cholesterol‐enriched high‐fat diet (western diet) in ApoE −/− mice; oxidative stress and inflammation were examined and intervened by supplement of Lycium ruthenium Murr. (LRM) extracts. LRM supplement did not influence body weight gain, food intake, and lipotoxicity of mice. LRM supplement significantly alleviated triglyceride accumulation in liver, with reduced inflammation, elevated GSH‐Px activity, and reduced MDA levels. The expression of fatty acids oxidative gene Scd1 was significantly increased, and fatty acids synthesis‐related gene Pparγ was dramatically downregulated on mRNA level in liver of mice with LRM supplement. These data demonstrated that LRM supplement decreased ROS production and inflammation, increased fatty acids oxidation, and reduced fatty acids synthesis in liver, leading to ameliorate the development of NAFLD induced by high western diet. Thus, oxidative stress and inflammation also are involved in the pathogenesis of western diet‐induced NAFLD, which is independent of obesity.
Highlights
Nonalcoholic fatty liver disease (NAFLD) is a manifestation of metabolic syndrome, which covers a spectrum of liver changes, from steatosis to a complex pattern with hepatocellular injury and inflammation in the absence of alcohol intake (Bedossa, 2017; Bellentani, 2017)
Our results showed that Lycium ruthenium Murr. (LRM) significantly reduced fatty acids accumulation due to increased oxidation and reduced synthesis, inflammation, and Reactive oxidative species (ROS) production in hepatocytes, resulting in alleviating nonalcoholic fatty liver disease in ApoE−/− mice, which is independent of obesity
The transcript level of anti-inflammatory Il-4 gene was dramatically increased in mice on Western Diet (WD) with LRM supplement compared with WD-fed mice (Figure 5c), while Il-10 mRNA level was similar in mice with or without LRM supplement (Figure 5d)
Summary
Nonalcoholic fatty liver disease (NAFLD) is a manifestation of metabolic syndrome, which covers a spectrum of liver changes, from steatosis to a complex pattern with hepatocellular injury and inflammation in the absence of alcohol intake (Bedossa, 2017; Bellentani, 2017). Cholesterol-induced NAFLD increases the risk of cardiovascular disease (CVD) and is often associated with atherosclerosis (Kim et al, 2014). Because cholesterol can be accumulated in arteries and liver, NAFLD induced by cholesterol overload accompanies by atherosclerosis in arteries. It is unknown if cholesterol-induced hepatic steatosis for further injury is similar to triglyceride-induced fatty liver. Our results showed that LRM significantly reduced fatty acids accumulation due to increased oxidation and reduced synthesis, inflammation, and ROS production in hepatocytes, resulting in alleviating nonalcoholic fatty liver disease in ApoE−/− mice, which is independent of obesity.
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