Non-Alcoholic Fatty Liver Disease: The Bile Acid-Activated Farnesoid X Receptor as an Emerging Treatment Target

Figure 2

Effect of FXR activation on triglyceride and cholesterol metabolism in the liver. FXR agonists result in a variety of responses modulating triglyceride (TG) and cholesterol metabolism. Activation of FXR inhibits triglyceride (TG)/fatty acid (FA) synthesis facilitated by suppressing sterol regulatory element-binding protein 1c (SREBP1c) via activation of short heterodimer partner (SHP). FXR controls assembly of very low-density lipoprotein (VLDL). FXR may increase the clearance of TG by stimulating lipoprotein lipase (LPL) activity as well as the hepatic uptake of remnants and low-density lipoprotein by inducing syndecan 1 (SDC1) and the VLDL receptor (VLDLR). FXR agonists may modulate LDL receptor activity via inhibition of proprotein convertase subtilisin/kexin 9 (PCSK9) and activate the reverse cholesterol transport pathway (RTC). FXR activation also impairs high-density lipoprotein (HDL) formation and suppresses cholesterol synthesis. apoA1, apoB, apoCII, apoCIII, apoAIV: apolipoprotein A1, B, CII, CIII, AIV; ANGTPL3: angiopoetin like 3; ABCG5/8: adenosine triphosphate binding cassette subfamily G member 5/8; CEH: cholesterylester hydrolase; HMGCR: 3-hydroxy-3-methylglutaryl coenzyme A reductase; MTP: microsomal triglyceride transfer protein; PON1: paraoxonase 1; SRBI: scavenger receptor B1; SCP2: sterol carrier protein 2.