Nonalcoholic fatty liver (NAFL) is an emerging global epidemic which progresses to nonalcoholic steatohepatitis (NASH) and cirrhosis in a subset of subjects. Various reviews have focused on the etiology, epidemiology, pathogenesis and treatment of NAFLD. This review highlights specifically the triggers implicated in disease progression from NAFL to NASH. The integrating role of genes, dietary factors, innate immunity, cytokines and gut microbiome have been discussed.
Keywords: AGE, Advanced glycation end products; ALT, Alanine aminotransferase; AMPK, AMP-activated protein Kinase; APPL1 and 2, Adaptor protein 1 and 2; ATP, Adenosine tri-phosphatase; BMI, Basal Metabolic Index; CD, Cluster of differentiation; COL13A1, Collagen, type XIII, alpha 1; DAMP, Damage assocauted molecular pattern molecules; EFCAB4B, EF-hand calcium binding domain 4B; FA, Fatty acid; FDFT1, Farnesyl-diphosphate farnesyltransferase 1; FFA, Free fatty acid; GCKR, Glucokinase regulatory protein; GLUT 5, Glucose transporter type 5; GWAS, Genome wide association studies; HDL, High density lipoprotein; HMGB1, High-mobility group protein B1; HOMA-IR, Homoestatic model assessment-insulin resistance; HSC, Hepatic Stellate Cells; Hh, Hedgehog; IL6, Interleukin 6; IR, Insulin Resistance; KC, Kupffer Cells; LPS, Lipopolysacharrides; LYPLAL1, Lypophospholipase like 1; MCP, Monocyte chemotactic protein; NAD, Nicotinamide adenine dinucleotide; NAFL, Nonalcoholic fatty liver; NAFLD, Nonalcoholic fatty liver disease; NASH, Nonalcoholic steatohepatitis; NCAN, Neurocan gene; NF-KB, Nuclear Factor Kappa B; NK, Natural Killer; NKL, Natural Killer T cells; NLR, NOD like receptor; NNMT, Nicotinamide N-methyltransferase gene; OXLAM, Oxidized linolenic acid metabolite; PAMP, Pathogen-associated Molecular pattern; PARVB, Beta Parvin Gene; PDGF, Platelet-derived growth factor; PNPLA3; PNPLA3, Patatin-like phospholipase domain-containing protein 3; PPAR-α, Peroxisome proliferator activated receptor alpha; PPP1R3B, Protein phosphatase 1 R3B; PUFA, Poly unsaturated fatty acid; PZP, Pregnancy-zone protein; ROS, Reactive oxygen species; SAMM, Sorting and assembly machinery component; SCAP, SREBP cleavage-activating protein; SFA, Saturated fatty acid; SNP, Single nucleotide polymorphism; SOCS3, Suppressor of cytokine signaling 3; SOD2, Superoxide dismutase 2 gene; SREBP-1C, Sterol regulatory Element—Binding Protein 1-C gene; TLR, Toll like receptor; TNF α, Tumor necrosis factor Alpha; UCP3, Uncoupling protein 3 gene; adiponectin; cytokines; gut microbiota; lipotoxicity.