Table 3.
Omics approaches for the in vitro modeling of NAFLD.
| Omics/ Technique |
Cell Model (NAFLD Induction) | Observations | Ref. |
|---|---|---|---|
| Transcriptomics | |||
| Microarray | HuH7 (NEFA) | Increased expression of interferon-stimulated genes and NF-kB-dependent pro-inflammatory genes | [116] |
| HLCs and HepG2 (NEFA) | Increase in the PPAR pathway genes and Perilipin-2 | [19] | |
| HepG2 and HSCs (NEFA) | Up-regulation in the ER-stress pathway genes | [117] | |
| PHH, HepG2, and HuH7 (NEFA and TNFα) | Comparison of different test systems. Changes in the genes linked with lipid droplet formation and metabolism (i.e., HSDL2) | [118] | |
| HLCs treated (NEFA, TNFα, IL1β, glucose, Insulin, and TGF1β) | Testing the anti-NASH compound (elafibranor). Gene expression profile and inflammatory markers of NASH | [88] | |
| RNASeq | 3D cocultures of PHH, HSCs, KC, and LSEC (NEFA, glucose, and TNFα) | Time course effects (3, 8, 10 days). 468 differentially expressed genes related to immune cell adhesion and inflammatory pathways | [71] |
| HepG2 (NEFA & TNFα) | Evaluation of lncRNAs profiling in a model of steatohepatitis | [119] | |
| HepG2 (NEFA) | Differential expression of lncRNAs in untreated and steatotic cells with and without treatment with exendin-4 | [120] | |
| Proteomics | |||
| HPLC-MS | C3A cells (lactate, pyruvate, octanoate, and ammonia) | 104 differentially expressed proteins as indicators of enhanced protein synthesis accompanied by a down-regulation of histones | [121] |
| NLC-MS | HepG2 (NEFA, and menadione) | Identification of the differentially expressed carbonylated proteins (i.e., ATP5A) in NASH | [122] |
| Metabolomics | |||
| GC-MS, UHPLC-MS | HepaRG (NEFA) | Global metabolomic analysis. Increased levels of branched chain amino acids and TCA cycle intermediates. Reduced carnitine and GSH levels | [43] |
| HPLC-MS | HepaRG (valproic acid) | Exposure to different concentrations and exposure times of VPA resulted in the identification of a typical steatotic profile: decreased carnitine, SAMe, and PEs in combination with the up-regulation of neutral heavy chain lipids | [123] |
| HPLC-MS | 3D PHH spheroids (NEFA, insulin, glucose, and fructose) | Identification of the metabolites up-regulated in steatosis after 7 and 21 days of treatment. Study of the response to drug treatments | [65] |
| HPLC-MS | HepG2 (NEFA and drugs) | Identification of phospholipidosis- and steatosis-specific metabolites (NEFA, acylcarnitines, monoacylglycerides, diacylglycerides, and TAG) after incubation with phospholipidogenic and steatogenic compounds | [124] |
| Combined strategy | |||
| Microarray & HPLC-MS | C3A (NEFA, lactate, pyruvate, octanoate, & ammonia) | Proteogenomics analysis revealed three candidate genes (fibrinogen α, β and γ chains) and their relation to cardiovascular risk associated with NAFLD patients | [125] |
| RNASeq & GC-MS (lipidomics) | HuH7 and PHH (NEFA, fructose, & insulin) | Studying the effects of media nutritional substrates on intracellular lipid accumulation by means of lipidomics (altered glucose metabolism, FA oxidation, and lipoprotein secretion) and transcriptomics | [126] |
| Microarray & UHPLC-MS | HLCs (lactate, pyruvate, & octanoate) | HLCs treated with lactate, pyruvate, and octanoate recapitulate the transcriptional and metabolic dysregulation of NAFLD The epigenomic analysis revealed the retained expression of TET enzymes and 5hmC | [97] |
| RNASeq & UHPLC-MS (lipidomics) | HPP, HSCs, and hMP (NEFA, glucose, & insulin) | The model recapitulated lipotoxic stress with a similar therapeutic drug response of NASH patients. High ATP and β-oxidation levels | [70] |