Non-alcoholic fatty liver disease (NAFLD) is a growing cause of chronic liver disease worldwide. It is characterised by steatosis, liver inflammation, hepatocellular injury and progressive fibrosis. Several preclinical models (dietary and genetic animal models) of NAFLD have deepened our understanding of its aetiology and pathophysiology. Despite the progress made, there are currently no effective treatments for NAFLD. In this review, we will provide an update on the known molecular pathways involved in the pathophysiology of NAFLD and on ongoing studies of new therapeutic targets.
Keywords: ACC, acetyl-CoA carboxylase; ASK1, apoptosis signal-regulating kinase 1; CAP, controlled attenuation parameter; ChREBP; ChREBP, carbohydrate responsive element–binding protein; FAS, fatty acid synthase; FFA, free fatty acid; FGF21, fibroblast growth factor-21; FXR; FXR, farnesoid X receptor; GGT, gamma glutamyltransferase; HCC, hepatocellular carcinoma; HFD, high-fat diet; HSC, hepatic stellate cells; HSL, hormone-sensitive lipase; HVPG, hepatic venous pressure gradient; IL-, interleukin-; JNK, c-Jun N-terminal kinase; LXR; LXR, liver X receptor; MCD, methionine- and choline-deficient; MUFA, monounsaturated fatty acids; NAFLD; NAFLD, non-alcoholic fatty liver disease; NASH; NASH, non-alcoholic steatohepatitis; NEFA; NEFA, non-esterified fatty acid; PPARα; PPARα, peroxisome proliferator-activated receptor-α; PUFAs, polyunsaturated fatty acids; PY, persons/years; Phf2, histone demethylase plant homeodomain finger 2; RCT, randomised controlled trial; SCD1, stearoyl-CoA desaturase-1; SFA, saturated fatty acid; SREBP-1c; SREBP-1c, sterol regulatory element–binding protein-1c; TCA, tricarboxylic acid; TLR4, Toll-like receptor 4; TNF-α, tumour necrosis factor-α; VLDL, very low-density lipoprotein; animal models; glucotoxicity; lipotoxicity.
© 2021 Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL).