Pathogenesis of fatty liver according to various etiologies (IMAGE)
Caption
(A) Due to PNPLA3 defects. Genetic defects in PNPLA3 result in decreased hydrolysis of triglycerides to fatty acids. This leads to increased intrahepatic triglycerides and decreased exportation of VLDL generating hepatic steatosis. (B) Due to TM6SF2 defects. Genetic defects in TM6SF2 decrease the hepatic export of VLDL. This increases intrahepatic triglycerides causing hepatic steatosis. (C) Due to ApoB defects. Genetic defects in ApoB result in decreased packaging of fatty acids in the ER leading to increased intrahepatic triglycerides and decreased hepatic export of VLDL giving rise to hepatic steatosis. (D) Due to LAL defects. Genetic defects in LAL result in decreased lysosomal breakdown of LDL into free cholesterol and fatty acids. This leads to increased intrahepatic LDL, upregulation of LDL receptors, and stimulation of HMGCoA-R with subsequent increased cholesterol production. ABCA1, ATP-binding cassette A1; ACAT, acetyl-coenzyme A acetyltransferase; ApoB, apolipoprotein B; DNL, de novo lipogenesis; ER, endoplasmic reticulum; FFAs, free fatty acids; GCKR, glucokinase regulator; HDL, high-density lipoprotein; HMGCoA-R, 3-hydroxy-3-methylglutaryl-CoA reductase; LAL, lysosomal acid lipase; LDL, low-density lipoprotein; LDL-R, low-density lipoprotein receptor; LXRs, liver X receptors; SREBPs, steroid regulation binding proteins; PNPLA3, palatine-like phospholipase domain-containing-3; TG, triglyceride; TM6SF2, transmembrane 6 superfamily member 2; VLDL, very low-density lipoprotein.
Credit
Jasmine Tidwell, George Y. Wu
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CC BY-NC