Ascorbic acid inhibits transcriptional activities of LXRα to ameliorate lipid metabolism disorder. (January 2022)

• Record Type: Journal Article
• Authors: Wang, Dandan; Yin, Zequn; Han, Lan; Zhang, Mengxue; Li, Huaxin; Yang, Xiaoxiao; Chen, Yuanli; Zhang, Shuang; Han, Jihong; Duan, Yajun
• Is Part Of: Journal of functional foods. Volume 88(2022)
• Publication Date: 2022-01
• Subjects: Ascorbic acid -- Triglyceride -- LXRα -- SREBP1c -- AMPKα; AA ascorbic acid -- TG triglycerides -- FFA free fatty acid -- NAFLD nonalcoholic fatty liver disease -- HFD high-fat diet -- LXRα liver X receptor α -- AMPKα AMP-activated protein kinase α -- PA palmitic acid -- OA oleic acid -- C.C Compound C -- FASN fatty acid synthase -- ACC1 acetyl-CoA carboxylase 1 -- SREBP1c sterol-responsive element binding protein 1c -- DGAT acyl-CoA: diacylglycerol acyltransferase -- SCD1 stearoyl-CoA desaturase 1 -- ATGL adipose triglyceride lipase -- CGI-58 comparative gene identification-58 -- HSL hormone-sensitive lipase -- MTTP microsomal triglyceride transfer protein -- GAPDH glyceraldehyde-3-phosphate dehydrogenase -- HSP90 heat shock protein 90; Functional foods -- Analysis -- Periodicals; Food -- Biotechnology -- Periodicals; Nutrition -- Periodicals; 613.2
• DOI: 10.1016/j.jff.2021.104901
• Languages: English
• ISSNs: 1756-4646

Abstract

Graphical abstract: Treatment of hepatocytes or mice with ascorbic acid inhibits FASN, ACC1 and SREBP1c expression which results in reduction of TG in hepatocytes. Mechanistically, ascorbic acid decreases cellular lipid accumulation in hepatocytes, which is related to the inhibition of LXRα nuclear translocation and activation of AMPKα. Highlights: Ascorbic acid reduces hepatic triglyceride synthesis. Ascorbic acid inhibits expression of LXRα-mediated lipogenic genes. Ascorbic acid inhibits LXRα nuclear translocation. Ascorbic acid inhibits LXRα nuclear translocation by activating AMPKα. Abstract: It has been reported that ascorbic acid inhibits non-alcoholic fatty liver disease partially by activating fatty acid β-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 α (LXRα) and AMP-activated protein kinase α (AMPKα), 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 LXRα nuclear translocation and activating AMPKα. In vivo, administration of ascorbic acid decreased triglyceride levels in serum and liver as well as FFA levels in the liver. Taken together, AMPKα/LXRα-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.