Betaine attenuates chronic alcohol-induced fatty liver by broadly regulating hepatic lipid metabolism

Abstract

Betaine has previously been demonstrated to protect the liver against alcohol-induced fat accumulation. However, the mechanism through which betaine affects alcohol-induced hepatic lipid metabolic disorders has not been extensively studied. The present study aimed to investigate the effect of betaine on alcoholic simple fatty liver and hepatic lipid metabolism disorders. A total of 36 rats were randomly divided into control, ethanol and ethanol + betaine groups. Liver function, morphological alterations, lipid content and tumor necrosis factor (TNF)-α levels were determined. Hepatic expression levels of diacylglycerol acyltransferase (DGAT) 1, DGAT2, sterol regulatory element binding protein (SREBP)-1c, SREBP-2, fatty acid synthase (FAS), 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase, peroxisome proliferator-activated receptor λ coactivator (PGC)-1α, adiponectin receptor (AdipoR) 1 and AdipoR2 were quantified. Serum and adipose tissue adiponectin levels were assessed using an enzyme-linked immunoassay. The results demonstrated that alcohol-induced ultramicrostructural alterations in hepatocytes, including the presence of lipid droplets and swollen mitochondria, were attenuated by betaine. Hepatic triglyceride, free fatty acid, total cholesterol and cholesterol ester contents and the expression of DGAT1, DGAT2, SREBP-1c, SREBP-2, FAS and HMG-CoA reductase were increased following ethanol consumption, however were maintained at control levels following betaine supplementation. Alcohol-induced decreases in hepatic PGC-1α mRNA levels and serum and adipose tissue adiponectin concentrations were prevented by betaine. The downregulation of hepatic AdipoR1 which resulted from alcohol exposure was partially attenuated by betaine. No significant differences in liver function, TNF-α, phospholipid and AdipoR2 levels were observed among the control, ethanol and ethanol + betaine groups. Overall, these results indicated that betaine attenuated the alcoholic simple fatty liver by improving hepatic lipid metabolism via suppression of DGAT1, DGAT2, SREBP-1c, FAS, SREBP-2 and HMG-CoA reductase and upregulation of PGC-1α.