Table 1.
The summary of the pain dissection of the FMGs signature.
| Gene | Association with fatty acid | Association with pain |
|---|---|---|
| FASN | FASN is a key enzyme regulating the de novo synthesis of fatty acids, which can catalyze acetyl-CoA and malonyl-CoA to produce palmitate. (PMID: 26519059) | Palmitate can activate NF-κB transcription factors and regulate the expression of NMDA receptor subunits. FASN can be used as a therapeutic target to reduce neuropathic pain. (PMID: 25855977) |
| ACOT9 | ACOT9 regulates fatty acid synthesis by catalyzing the hydrolysis of fatty acyl-coenzyme A to form free fatty acid (FFA) and coenzyme A (CoA). (PMID: 36004563) | NA |
| MID1IP1 | The change of MID1IP1 expression can affect the expression of fatty acid synthase (FASN) and induce phosphorylation of Acetyl-CoA carboxylase (ACC), thereby affecting the biosynthesis of fatty acids and triglycerides. (PMID: 34153683, 35916211) | NA |
| CYP2C9 | CYP2C9 is a cytochrome P450 enzyme that has cyclooxygenase activity and catalyzes the oxidation of polyunsaturated fatty acid arachidonic acid to eicosatrienoic acids. (PMID: 30012669) | CYP2C9 can predict the analgesic effect of tramadol and ketorolac. (PMID: 34246203) |
| ABCD1 | ABCD1 gene encodes peroxisome transport protein, which is involved in transporting saturated very long chain fatty acids to peroxidase for β-oxidation. (PMID: 32017990) | Absence of ABCD1 will lead to mechanical allodynia mediated by mechanosensitive ion channels and dysfunction of satellite glial cells. (PMID: 35681537) |
| CPT2 | Fatty acid oxidation (FAO) is a process in which carnitine palmitoyltransferase 1 and 2 (CPT1 and CPT2) transport long-chain fatty acids to the mitochondrial matrix, and then oxidize them to acetyl-CoA, NADH and FADH2 and generate energy. (PMID: 33027638) | CPT2 deficiency may lead to metabolic disorder in the body, causing patients to have diffuse muscle pain symptoms. (PMID: 27034144) |
| CRAT | Carnitine acetyltransferase (CRAT) is the basic enzyme in carnitine metabolism, which regulates the metabolic flexibility of muscle and increases exercise ability. Carnitine can promote fatty acids to enter mitochondria for oxidative decomposition during fat metabolism, which is helpful to promote the balance of fat metabolism. (PMID: 29444428) | NA |
| TP53INP2 | TP53INP2 mediates peroxisome proliferator-activated receptor gamma (PPARG) regulates macroautophagic/autophagic-dependent mechanism that induce brown fat differentiation and thermogenesis. (PMID: 35947488) | NA |
| FAAH2 | Fatty acid amide hydrolase (FAAH1 and FAAH2) can inactivate endogenous cannabinoid, and monoacylglycerol lipase can hydrolyze to 2-arachidonic glycerol. (PMID: 30070030) | Fatty acid amide hydrolase (FAAH) plays an important role in the hydrolysis and inactivation of endogenous arachidonic ethanolamide (AEA). AEA can protect neurons from inflammatory injury by activating cannabinoid receptors (CB1R and CB2R) and transient receptor TRPV1. FAAH inhibitors may become a safe and reliable new analgesic. (PMID: 34364309, 29017758) |
| PTPRG | PTPRG is a negative regulator of insulin signal transduction, and insulin can promote the synthesis and storage of fat and reduce free fatty acids in blood. (PMID: 29180649) | NA |
NA, missing references.