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. 2022 Feb 21;135(10):1172–1181. doi: 10.1097/CM9.0000000000002092

Figure 2.

Figure 2

Molecular mechanisms of NAFLD. NAFLD is a complex and multifactorial disease. The development and progression of NAFLD is affected by insulin resistance, genetic polymorphisms, gut microbiota, race, gender, etc. Under insulin resistance or diabetes, the influx of FFAs from adipose tissue as well as DNL is increased. FFAs, particularly saturated FFAs, can cause ER stress, oxidative stress, apoptosis, and inflammasome activation via lipotoxic lipids (LPCs, ceramides, DAG, etc.). Cholesterol crystals also promote inflammasome activation. The change in the gut barrierallows LPS from gut microbiota to enter the portal circulation and activate toll-like receptors or inflammasome (pyroptosis) for induction of inflammation. The change in other gut microbiota products (ethanol, secondary bile acids, etc.) may also contribute to the development of NAFLD. ApoB: Apolipoprotein B; BAs: Bile acids; chREBP: Carbohydrate response element-binding protein; DNL: de novo lipogenesis; DAG: Diacylglycerols; ER: Endoplasmic reticulum; FC: Freecholesterol; FAO: Fatty acid oxidation; FFAs: Free fatty acids; GCKR: Glucokinase regulatory; HSD17B13: Hydroxysteroid 17-beta dehydrogenase 13; LPS: Lipopolysaccharides; LPC: Lysophosphatidylcholine; MBOAT7: Membrane-bound O- acyltransferase domain-containing 7; NAFLD: Nonalcoholic fatty liver disease; PPP1R3B: Protein phosphatase 1 regulatory subunit 3B; PNPLA3: Palatin-like phospholipase domain containing 3; SREBP-1c: Sterol regulatory element-binding protein 1c; TM6SF2: Transmembrane 6 superfamily 2.