Table 2.
Ability of various lipids to promote or inhibit tumour growth in HCC and CCA.
| Lipid | Impact | Mechanism | Ref |
|---|---|---|---|
| Fatty acids | |||
| SFA | Telomere shortening in obesity | Increase DNA methylation in TERT promoter | 123,165 |
| Oleic acid | Promote HCC | deregulate p53 signalling via miR21-HBP1 axis | 132,168 |
| Palmitoleic acid (16:1) | Promote HCC | Rising lipolysis and increased oxidative stress via mitochondrial beta oxidation, as well as increases insulin sensitivity, Wnt and TGFβ activation | 117,118 |
| Linoleic acid (18:2) | Promote NAFLD-HCC | Linoleic acid upregulates CPT1 to induce CD4(+) T cell apoptosis, hence mitochondrial function disruption along with increased FADS2 expression in tumours | 96,97,118 |
| Vaccenic and erucic acid | Promote NAFLD-HCC | Upregulation of SCD and ELOVL6 causes upregulation of these fatty acids | 117 |
| n-3 PUFA | Inhibit CCA | n-3 PUFAs suppressed c-Myc and inhibits CCA tumour growth | 171 |
| EPA, DHA |
Inhibit HCC |
Simultaneous inhibition of COX-2 and beta-catenin |
313 |
| Glycerophospho-lipids | |||
| Cardiolipin |
Promote HCC |
mTORC2 promotes cardiolipin synthesis, leading to accumulation in liver and then tumorigenesis, most probably via enhanced oxidative phosphorylation |
124 |
| Phospholipids | |||
| LPA (16:0) | Promote HCC | LPCs are metabolized by phospholipase D to produce LPAs that are potent mitogens, mediating their tumorigenic effect by the PI3K/AKT/mTOR signalling pathway or p38 MAPK signalling pathway | [175], [176], [177],314 |
| LPC (20:4) | Inhibit HCC | Low LPC indicate inflammatory and oxidative stress, through apoptosis induction through the death ligands (Fas and/or TNF-alpha) pathway | 135,178 |
| MUFA-PC |
Promote HCC |
Increased lipogenesis, fatty acyl desaturation, de novo synthesis of PC, and PC remodeling and decreased β-oxidation |
134 |
| Sphingolipids | |||
| S1P | Promote HCC and CCA | S1P activates YAP, PI3K/AKT and TFG-β1 production in HCC cells | [125], [126], [127], [128] |
| Glucosylceramide | Promote HCC | mTORC2 promotes glucosylceramide accumulation which increases tumorigenesis | 124 |
| (SM) 18:2/24:1 | Promote HCC | Enrichment might be due to a specific diet; more studies are needed | 123,135 |
| C16 | Promote HCC | Long-chain ceramides may have proliferative effects for HCC, RAS activation, regulatory ligand of p53 | 123,135,172 |
| C12:0, 16:0, 18:1 and 24:1 ceramides |
Promote HCC |
Associated with cannabinoid receptor activation and SCD downregulation |
132 |
| Sterols | |||
| Cholesteryl ester | Promote NAFLD-HCC | PTEN/PI3K/AKT/mTOR signalling pathway is responsible for cholesteryl ester accumulation which then leads to tumorigenesis | 249 |
| Cholesterol | Promote HCC | Upregulation of TAZ to promote fibrotic NASH | 114,249 |
CCA, cholangiocarcinoma; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; HCC, hepatocellular carcinoma; LPA, lysophosphatidic acid; LPC, lysophosphatidylcholine; MUFA, monounsaturated fatty acid; NASH, non-alcoholic steatohepatitis; PC, phosphatidylcholine; PUFA, polyunsaturated fatty acid; S1P, sphingosine-1-phosphate; SM, sphingomyelin.