title: Isocaloric Pair-Fed High-Carbohydrate Diet Induced More Hepatic Steatosis and Inflammation than High-Fat Diet Mediated by miR-34a/SIRT1 Axis in Mice.
abstract: To investigate the different effects of isocaloric high-fat diet (HFD) and high-carbohydrate diet (HCD) on hepatic steatosis and the underlying mechanisms, especially the role of microRNA-34a/silent information regulator T1 (SIRT1) axis, C57BL/6J mice (n = 12/group) were isocaloric pair-fed with Lieber-DeCarli liquid diet containing either high fat (HFLD) or high carbohydrate (HCLD) for 16 weeks. As compared to the HFLD fed mice, despite the similar final body weights, HCLD feeding: (1) induced more severe hepatic steatosis; (2) up-regulated hepatic expression of miR-34a accompanied with significant decrease of SIRT1 and nicotinamide phosphoribosyltransferase (NAMPT), SIRT1 activity and phosphorylation of AMPK; (3) up-regulated de novo lipogenesis (DNL) related proteins expression (ACC, SCD1), and down-regulated expressions of miR-122, miR-370 and miR-33; (4) decreased mRNA expressions of genes Cpt1, Pparα and Pgc1α related to fatty acid oxidation; (5) increased hepatic total cholesterol concentration and decreased expression of cholesterol metabolism related genes Abcg5, Abcg8, Abcg11, Cyp7a1 and Cyp8b1; and (6) induced higher hepatic inflammatory response accompanied with significant increased mRNA expressions of Il1β, Tnfα and Mcp1. Thus, isocaloric HCLD feeding induced greater severity in hepatic steatosis and inflammatory response than HFLD feeding, potentially through miR-34a/SIRT1 axis mediated promotion of DNL, inhibition of fatty acid oxidation and cholesterol metabolism.
authors.affiliation: Nutrition and Cancer Biology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA, 02111.|School of Public Health, Medical College of Soochow University, Suzhou, Jiangsu, China, 215123.
authors.forename: Xinli
authors.initials: X
authors.lastname: Li
authors.affiliation: Nutrition and Cancer Biology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA, 02111.
authors.forename: Fuzhi
authors.initials: F
authors.lastname: Lian
authors.affiliation: Nutrition and Cancer Biology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA, 02111.
authors.forename: Chun
authors.initials: C
authors.lastname: Liu
authors.affiliation: Nutrition and Cancer Biology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA, 02111.
authors.forename: Kang-Quan
authors.initials: KQ
authors.lastname: Hu
authors.affiliation: Nutrition and Cancer Biology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA, 02111.
authors.forename: Xiang-Dong
authors.initials: XD
authors.lastname: Wang
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D002784:Cholesterol / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects*; D004040:Dietary Carbohydrates / Q000009:adverse effects*; D005234:Fatty Liver / Q000097:blood / Q000139:chemically induced* / Q000150:complications* / Q000235:genetics; D005247:Feeding Behavior; D007249:Inflammation / Q000097:blood / Q000150:complications* / Q000235:genetics; D050356:Lipid Metabolism / Q000235:genetics; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D054409:Nicotinamide Phosphoribosyltransferase / Q000378:metabolism; D009929:Organ Size; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D004040:Dietary Carbohydrates; C551848:MIRN34a microRNA, mouse; D035683:MicroRNAs; D012333:RNA, Messenger; D002784:Cholesterol; D054409:Nicotinamide Phosphoribosyltransferase; D000263:Adenylate Kinase; D056564:Sirtuin 1