|
| Cell | Molecular target | Biological effect |
|
| HIF1α |
|
Hepatocyte | ↑ Lipid droplet binding protein adipose
differentiation-related protein (ADFP) | ↑ Triglyceride storage in lipid droplets [60] |
| ↑ Stearoyl-coenzyme A desaturase 1 (SCD-1) | ↑ De novo lipogenesis [61] |
↑ Enolase 1
↑ Lactate dehydrogenase 1 | ↑ Glycolysis
↑ Pyruvate metabolism [62] |
| ↑ Membrane glucose transporter- (GLUT-) 1 and GLUT-3 | ↑ Glucose uptake [63] |
↑ Plasminogen activator inhibitor- (PAI-) 1
↑ Platelet-derived growth factor- (PDGF-) A and PDGF-B | ↑ Hepatic stellate cell activation and fibrogenesis [64] |
| Hepatic stellate cells | ↑ PDGF-B
↑ Transforming growth factor- (TGF-) β1
↑ Vascular endothelial growth factor (VEGF)
↑ Chemokine receptor- (CCR-) 1 and 5 | ↑ Fibrogenesis
↑ Angiogenesis
↑ Carcinogenesis [31] |
| Kupffer cells | ↑ Plasminogen activator inhibitor- (PAI-) 1
↑ Platelet-derived growth factor- (PDGF-) A and PDGF-B | ↑ Hepatic stellate cell activation and fibrogenesis [65] |
|
| HIF2α |
| Hepatocyte | ↑ Lipid droplet binding protein adipose
differentiation-related protein (ADFP) | ↑ Triglyceride storage in lipid droplets [62] |
↓ Acyl-coenzyme A synthase long-chain family member 1
↓ Carnitine-palmitoyltransferase I | ↓ Mitochondrial fatty acid β-oxidation [62] |
↓ Acyl-CoA oxidase (Aco)
↓ Carnitine O-octanyltransferase | ↓ Peroxisomal fatty acid β-oxidation [62] |
| ↑ Membrane fatty acid transporter cluster differentiation 36 (CD36) | ↑ Fatty acid uptake from plasma [30] |
Sterol-regulatory-element binding protein-1c (Srebp-1c)
Fatty acid synthase (Fas)
Acetyl-CoA carboxylase (Acc)
(↑ early after HIF2α activation and then
↓ after long-term HIF2α activation) | De novo lipogenesis
(↑ early after HIF2α activation and then
↓ after long-term HIF2α activation) [30, 62] |
| ↑ Angiopoietin-like 3 (Angptl3) | ↓ Tissue lipoprotein lipase activity
↓
↑ Plasma triglycerides [62, 66] |
↓ Phosphoenolpyruvate-carboxykinase (Pepck)
↓ Glucose-6-phosphatase | ↓ Gluconeogenesis [62, 67] |
↓ Peroxisome proliferator-activated receptor γ
coactivator 1α (Pgc-1α)
↓ Hepatocyte nuclear factor 4 (Hnf4) | ↓ Gluconeogenesis [62, 67]
↓ Mitochondrial fatty acid β-oxidation [62] |
↑ Interleukin-1β
↑ Interleukin-6 | ↑ Inflammation [30] |
| Macrophage | ↑ Interleukin-1β
↑ Interleukin-6 | ↑ Inflammation [30] |
| Hepatic stellate cells | ↑ Lysyl oxidase-like- (LOXL-) 1 and LOXL-2
↑ Prolyl 4-hydroxylase α- (P4HA-) 1 and P4HA-2
↑ Procollagen lysine
↑ 2-Oxoglutarate 5-dioxygenase 2 (PLOD2)
↑ Transglutaminase 2 (TGM2) | ↑ Collagen synthesis and deposition
↑ Fibrogenesis [30] |
|
