1. Methyl-donor supplementation in obese mice prevents the progression of NAFLD, activates AMPK and decreases acyl-carnitine levels
- Author
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Christian Scherling, Rima Obeid, Jürgen Geisel, Hannelore Daniel, Stefanie Worsch, Bernhard L. Bader, Manuela Sailer, Jarlei Fiamoncini, Christoph Dahlhoff, Björn Hummel, and Kirsten Uebel
- Subjects
Hepatic steatosis ,ACC, acetyl-CoA carboxylase ,HFMS, methyl-donor supplemented high-fat diet ,3-HB, β-hydroxybutyrate ,LDL, low density lipoprotein ,PC, phosphatidylcholine ,Cbs, cystathionine β-synthase ,HF, high-fat diet ,AMP-activated protein kinase ,ANT, adenine nucleotide translocase ,Beta oxidation ,chemistry.chemical_classification ,biology ,C1, one-carbon ,Fatty liver ,VAT, visceral adipose tissue ,SAM, S-adenosylmethionine ,One-carbon metabolism ,TG, triacylglycerol ,ddc ,Fatty acid synthase ,Pemt, phosphatidylethanolamine methyltransferase ,Original Article ,β-HAD, β-hydroxyacyl CoA dehydrogenase ,medicine.drug ,MDS, methyl-donor supplementation ,NAFLD, non-alcoholic fatty liver disease ,medicine.medical_specialty ,GNMT, glycine N-methyltransferase ,C, control diet ,Fasn, fatty acid synthase ,HSP90, heat shock protein 90 ,Gapdh, glyceraldehyde 3-phosphate dehydrogenase ,MTR, methionine synthase ,VLDL, very low density lipoprotein ,Internal medicine ,NEFA, non-esterified fatty acids ,medicine ,Obesity ,Carnitine ,SREBP1c, sterol regulatory element-binding protein-1c ,Bhmt, betaine-homocysteine methyltransferase ,Molecular Biology ,Acyl-carnitines ,Cpt1a, carnitine palmitoyltransferase-1a ,SM, sphingomyelin ,CACT, carnitine-acylcarnitine transporter ,SAH, S-adenosylhomocysteine ,Fatty acid ,AMPK ,DIO, diet-induced obesity ,PL, phospholipids ,Cell Biology ,Hcy, homocysteine ,medicine.disease ,AMPK, AMP-activated protein kinase ,Endocrinology ,PPARα, peroxisome proliferator-activated receptor-α ,chemistry ,MAT, methionine adenosyltransferase ,HMW adiponectin, high molecular weight adiponectin ,Hprt1, hypoxanthine phosphoribosyltransferase 1 ,MCD, malonyl-CoA decarboxylase ,biology.protein ,β-oxidation ,PGC1α, peroxisome proliferator-activated receptor-γ co-activator-1α ,CMS, methyl-donor supplemented control diet ,Steatosis - Abstract
Non-alcoholic fatty liver disease (NAFLD) results from increased hepatic lipid accumulation and steatosis, and is closely linked to liver one-carbon (C1) metabolism. We assessed in C57BL6/N mice whether NAFLD induced by a high-fat (HF) diet over 8 weeks can be reversed by additional 4 weeks of a dietary methyl-donor supplementation (MDS). MDS in the obese mice failed to reverse NAFLD, but prevented the progression of hepatic steatosis associated with major changes in key hepatic C1-metabolites, e.g. S-adenosyl-methionine and S-adenosyl-homocysteine. Increased phosphorylation of AMPK-α together with enhanced β-HAD activity suggested an increased flux through fatty acid oxidation pathways. This was supported by concomitantly decreased hepatic free fatty acid and acyl-carnitines levels. Although HF diet changed the hepatic phospholipid pattern, MDS did not. Our findings suggest that dietary methyl-donors activate AMPK, a key enzyme in fatty acid β-oxidation control, that mediates increased fatty acid utilization and thereby prevents further hepatic lipid accumulation.
- Published
- 2014