Ascorbic acid inhibits transcriptional activities of LXRα to ameliorate lipid metabolism disorder

摘要

It has been reported that ascorbic acid inhibits non-alcoholic fatty liver disease partially by activating fatty acid beta-oxidation. However, little is known about the mechanism of ascorbic acid-mediated lipid synthesis. Western blot, qRT-PCR and immunofluorescent staining were used to determine if ascorbic acid can regulate expression of liver X receptor alpha (LXR alpha) and AMP-activated protein kinase alpha (AMPK alpha), which are key regulators of lipogenic genes. In hepatocytes, ascorbic acid decreased cellular lipid accumulation. Mechanistically, ascorbic acid inhibited expression of the genes for lipid synthesis by reducing LXR alpha nuclear translocation and activating AMPK alpha. In vivo, administration of ascorbic acid decreased triglyceride levels in serum and liver as well as FFA levels in the liver. Taken together, AMPK alpha/LXR alpha-mediated reduction of lipid accumulation in the liver is a novel activity of ascorbic acid on lipid metabolism, suggesting that ascorbic acid is an effective and safe dietary supplement to ameliorate hypertriglyceridemia.

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