Table 1. Molecular Factors Promote Nonalcoholic Fatty Liver Disease/ Non-Alcoholic Steato-Hepatitis a.
| Molecular Factors Promote NAFLD/NASH | Causes Induction | Effects | References |
|---|---|---|---|
| NF-κB | Hepatic Steatosis IKKβ | TNF-a, Fas ligand, TGF-b, IL-8, leptin, adiponectin, IL-6, IL-1b | Cai et al. (17) |
| Activation of Kupffer cells and macrophages | |||
| Apoptosis/inflammation. | |||
| IR | |||
| TNF-a (and T-1031C/C-856A) | Fat-engorged adipocytes Kupffer cells | Hepatic mitochondrial permeability | Cai et al. (17) Takaki et al. (12), Reinehr T et al. (19) |
| B-oxidation | |||
| Release cytochrome c | |||
| Increase of electron delivery to the mitochondrial respiratory chain | |||
| Lipolysis and hepatic lipogenesis | |||
| Amplify hepatic synthesis of FA | |||
| Interferes on IRS-2 proteins, causing IR | |||
| Inhibits adiponectin expression | |||
| Promote secretion of leptin | |||
| IL-1 | Th-1, TLR-9 | Promote secretion of leptin | Cai et al. (17) Roh et al. (20) |
| IR | |||
| Hepatic fat accumulation | |||
| Acts on HSC to induce liver fibrosis | |||
| IL-2 | Th-1a | IR | Seth et al. (21) |
| IL-6 (and 174G/C) | NF-κBa | Lipolysis | Carulli et al. (22), Reinehr T et al. (19) |
| Amplify hepatic synthesis of FA | |||
| MetS | |||
| IL-8 | NF-κBa | Activation of Kupffer cells and macrophages | Cai et al. (17) |
| Apoptosis | |||
| Inflammation | |||
| TGF-b5 | NF-κB2 | Activation of Kupffer cells and macrophages | Cai et al. (17) |
| Apoptosis | |||
| Inflammation | |||
| IFN-a | Th-1 | IR | Seth et al. (21) Pacifico et al. (23) |
| Proatherogenic effects | |||
| HMGB1 | Hepatocytes | Inflammation | Salpietro C et al. (24), Lin YC et al. (25), Arrigo et al. (26) |
| Increased TLR-4 | |||
| Fibrosis | |||
| TLR-2 | Expressed on monocytes, myeloid dendritic cells or mast cells | Inflammation. | Roh et al. (20) Salpietro C et al. (27) |
| Fibrosis | |||
| TLR-4 | HMGB1 | Inflammation | Roh et al. (20) |
| Fibrosis | |||
| TLR-9 | Expressed on Kupffer cells | Promote release IL-1b | Takaki et al. (12) |
a Abbreviations: FA, fatty acids; HMGB1, high mobility group protein B1; HSC, hepatic stellate cell; IKK-B, inhibitory- kappa B; IL, interleukin; INF-a, interferon-alpha; IR, insuline resistance; IRS-2, insulin receptor substrate-2; MetS, metabolic syndrome; NAFLD, nonalcoholic fatty liver disease; NASH, non-alcoholic steato-hepatitis; NK-κB, nuclear factor- kappa B; TGF-b, transforming growth factor- beta; Th-1, T-helper-1; TLR, toll like receptor; TNF-a, Tumor necrosis factor-alpha.