Preventive effects of betaine supplementation on the development of non‐alcoholic fatty liver in rats

Non‐alcoholic fatty liver disease represents a wide spectrum of liver diseases, ranging from simple fat accumulation through steatosis with inflammation, necrosis, and ultimately to cirrhosis. Hepatic fat accumulation is known to play a critical role in the disease initiation and progression. We examined the effects of betaine on the development of non‐alcoholic fatty liver. Male rats were provided with a high fat liquid diet or a high fat diet supplemented with betaine (1 %) for 3 wk. Betaine supplementation reduced hepatic triglyceride significantly while increasing the total cholesterol and triglyceride levels in blood. Betaine supplementation increased mRNA expressions of acetyl CoA carboxylase (ACC), fatty acid synthase (FAS), and glycerol phosphate acyl transferase significantly. Protein levels of FAS and total ACC were also increased. Liver X receptor‐á and nuclear form of sterol regulatory binding protein‐1c (nSREBP‐1c) were decreased, but the precursor form of SREBP‐1c was not altered in the rats fed betaine. Activation of AMP‐activated protein kinase (AMPK) as well as phosphorylation of ACC was enhanced significantly by betaine intake. The present results suggest that both enhancement of lipid secretion from liver to blood and inhibition of hepatic lipid synthesis via activation of AMPK may play significant roles in the prevention of fat accumulation in the liver of rats supplemented with betaine.