Methods We exposed HLCs to LPO for 48hours to induce lipid accumulation. We characterised the transcriptome using RNA-seq, the metabolome using ultra-performance liquid chromatography-mass spectrometry and the epigenome using 5-hydroxymethylation DNA immunoprecipitation (hmeDIP) sequencing.
Results LPO exposure induced a NAFLD phenotype in HSCs with transcriptional and metabolomic dysregulation consistent with those present in human NAFLD. HLCs maintain expression of the Tet enzymes and have a liver-like epigenome. LPO induced 5hmC enrichment at lipid synthesis and transport genes.
Conclusions HLCs treated with LPO recapitulate the transcriptional and metabolic dysregulation seen in NAFLD and additionally retain Tet expression and 5hmC. This in vitro model of NAFLD will be useful for future mechanistic and therapeutic studies.
|Journal||Philosophical Transactions of the Royal Society of London Series B|
|Early online date||21 May 2018|
|Publication status||Published - 5 Jul 2018|