Luteolin Ameliorates Nonalcoholic Fatty Liver Disease via Regulation of Hepatic Lipid Uptake, Autophagy, and Apoptosis in WD/CCl4-induced Mice

Abstract

Background and Purpose Nonalcoholic fatty liver disease (NAFLD) is a worldwide health problem with high prevalence and morbidity associated with obesity, insulin resistance, type 2 diabetes mellitus (T2DM), and dyslipidemia. Luteolin is a natural flavonoid with various activities. We aimed to investigate whether luteolin can alleviate NAFLD and its possible mechanism. Methods A mouse model with NAFLD was induced by Western diet (WD) and carbon tetrachloride (CCl4) injection. Twenty-four mice were distributed into three groups randomly: Normal diet group (CON, n = 8), NAFLD group (NAF, n = 8), and luteolin group (LUT, n = 8). NAFLD model was induced by feeding mice in NAF and LUT groups with WD and injecting CCl4. CON group were fed with a normal diet in the same period. The LUT group was administered orally with luteolin (20 mg/kg) every day, starting from the 1st day of the 5th week for 8 weeks, while the CON group was treated with a vehicle. Throughout the experiment, body weight, lipid profile, glucose tolerance test, and the hepatic expressions of CD36/FABP1/LC3B/Bcl-2 were measured beside the histopathological examination. Results Luteolin treatment effectively prevents the body from weight gain in mice with NAFLD (NAF vs. LUT: 36.0 g vs. 32.4 g, p < 0.05). Serum total cholesterol and triglyceride levels are both significantly increased in the NAF group ( p < 0.01) and reduced to some extent in the LUT group ( p < 0.05). Oral glucose tolerance test (OGTT) test results show that luteolin could improve the impaired glucose tolerance and downregulate the elevated fasting blood glucose in mice with NAFLD ( p < 0.05). Histopathological results demonstrate luteolin reduces hepatic steatosis and hepatic fibrosis in NAFLD mice. The possible mechanisms may include that luteolin decreases hepatic CD36 and FABP1 expression, and increases levels of autophagy marker LC3B and antiapoptotic protein Bcl-2. Conclusion Luteolin could reduce hepatic steatosis and fibrosis, hyperglycemia, body weight, and serum lipid levels in NAFLD mice, which exhibits huge potential in the treatment of metabolic disorders related to NAFLD.