Table 3.
The main hepatokines and adipokines and their mechanisms in the development of non-alcoholic fatty liver disease.
| Organokine (main source and target tissue) | Liver lipogenesis and metabolic syndrome (effect, mechanism) | Liver inflammation (effect, mechanism) | Liver fibrosis (effects, mechanism) |
|---|---|---|---|
| Adiponectin (adipose tissue, liver) (41, 76, 91–94) | Liver lipogenesis; DNL; FA β-oxidation; PPAR-α expression; Gluconeogenesis; Insulin resistance; Oxidative stress; SIRT-1 activity; SREBP-1 expression; | Liver inflammation; TNF-α/IL6 expression; NF-κB expression; IL-10 expression; AMPK activity; | Liver fibrosis; HSCs activity; TGF-β expression; JNK inhibition |
| Leptin (adipose tissue, distributed and active in various tissues including liver) (41, 93, 95–97) | Liver lipogenesis; FA β-oxidation; PPAR-α activation; Insulin resistance; mTOR activity; SREBP-1/ChREB expression; Adipogenesis; | Liver inflammation; CD14 expression on KCs; STAT-3 activation; | Liver fibrosis; HSCs activity; TGF-β expression; JAK-STAT pathway; HCC risk; |
| Resistin (adipose tissue, inflammatory cells including KCs, HSCs; hepatocytes) (92 , 98–107) | Liver lipogenesis; Adipogenesis; Insulin resistance; SREPB-1/ChREBP expression; MetS risk | Liver inflammation; TNF-α/IL6 expression; TLR4/NF-kB-mediated pathway | Liver fibrosis; HSCs activity; TGF-β synthesis; NF-kB signalling; |
| Ghrelin (entero-endocrine cells, stomach, pancreas) (39, 92, 108–110) | Liver lipogenesis; TG serum level; Adipogenesis; T2D risk; Insulin resistance; | Liver inflammation; NF-κB activation; TLR4 expression; IL-10 synthesis; mTOR/PPARγ signalling; | Liver fibrosis; TGF-β synthesis; NF-κB signalling; |
| FGF 21 (liver/effect on adipose tissue, less other tissues) (111–113 , 114–117) | Liver lipogenesis; FA β-oxidation; mTOR activity; PPAR-α/γ.> Insulin resistance; Adipolysis< Dyslipidemia; | Liver inflammation; NF-κB activation; | Liver fibrosis; TGF-β synthesis; |
| Fetuin A (hepatocytes) (51, 118–122) | Liver lipogenesis; Adipogenesis; SREBP1c; Insulin resistance; T2D risk; Dyslipidemia; | Liver inflammation*; Endogenous ligand between FA and TLR4 TLR4 signaling; NF-κB activation; | Liver fibrosis*; TGF-β activity; |
| Chemerin (adipose tissue, liver; receptors in various tissues) (102, 123–125) | Liver lipogenesis; Adipogenesis; Insulin resistance; | Liver inflammation*; IL-6 expression; | Liver fibrosis; TGFβ1 synthesis; |
| Visfatin (adipocytes, hepatocytes, muscle cells, leukocytes) (92, 126–128) | Liver lipogenesis*; Adipogenesis; Insulin resistance; * | Liver inflammation*; TNF-α/IL-6 synthesis; STAT3/NF-κB pathways; | Liver fibrosis*; |
| Selenoprotein P (cellular enzymes with antioxidant properties) (129–132) | Liver lipogenesis; Adipogenesis; Insulin resistance; Obesity;, T2D risk | Liver inflammation*; | Liver fibrosis*; |
DNL, de novo lypogenesis; T2D, Type 2 diabetes; FA, fatty acids; HC, hepatocarcinoma; KCs, Kupffer cells; HSCs, hepatic stellate cells; MetS, metabolic syndrome; *controversial role, conflicting data.