%0 Electronic Article %A Liu, Jun and Tang, Tao and Wang, Guo-Dong and Liu, Bo %I Portland Press Ltd. %D 2019 %D 2019 %G English %@ 0144-8463 %@ 1573-4935 %~ Hochschule Zittau / Görlitz, Hochschulbibliothek %T LncRNA-H19 promotes hepatic lipogenesis by directly regulating miR-130a/PPARγ axis in non-alcoholic fatty liver disease %V 39 %J Bioscience Reports %V 39 %N 7 %U http://dx.doi.org/10.1042/bsr20181722 %X Abstract Background: As one of the most common liver disorders worldwide, non-alcoholic fatty liver disease (NAFLD) begins with the abnormal accumulation of triglyceride (TG) in the liver. Long non-coding RNA-H19 was reported to modulate hepatic metabolic homeostasis in NAFLD. However, its molecular mechanism of NAFLD was not fully clear. Methods: In vitro and in vivo models of NAFLD were established by free fatty acid (FFA) treatment of hepatocytes and high-fat feeding mice, respectively. Hematoxylin and Eosin (H&E) and Oil-Red O staining detected liver tissue morphology and lipid accumulation. Immunohistochemistry (IHC) staining examined peroxisome proliferator-activated receptor γ (PPARγ) level in liver tissues. ELISA assay assessed TG secretion. Luciferase assay and RNA pull down were used to validate regulatory mechanism among H19, miR-130a and PPARγ. The gene expression in hepatocytes and liver tissues was detected by quantitative real-time PCR (qRT-PCR) and Western blotting. Results: H19 and PPARγ were up-regulated, while miR-130a was down-regulated in NAFLD mouse and cellular model. H&E and Oil-Red O staining indicated an increased lipid accumulation. Knockdown of H19 inhibited steatosis and TG secretion in FFA-induced hepatocytes. H19 could bind to miR-130a, and miR-130a could directly inhibit PPARγ expression. Meanwhile, miR-130a inhibited lipid accumulation by down-regulating NAFLD-related genes PPARγ, SREBP1, SCD1, ACC1 and FASN. Overexpression of miR-130a and PPARγ antagonist GW9662 inhibited lipogenesis and TG secretion, and PPARγ agonist GW1929 reversed this change induced by miR-130a up-regulation. Conclusion: Knockdown of H19 alleviated hepatic lipogenesis via directly regulating miR-130a/PPARγ axis, which is a novel mechanistic role of H19 in the regulation of NAFLD. %Z https://katalog.hszg.de/Record/ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTA0Mi9ic3IyMDE4MTcyMg %U https://katalog.hszg.de/Record/ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTA0Mi9ic3IyMDE4MTcyMg