Lipids are a complex and diverse group of molecules with crucial roles in many physiological processes, as well as in the onset, progression, and maintenance of cancers. Fatty acids and cholesterol are the building blocks of lipids, orchestrating these crucial metabolic processes. In the liver, lipid alterations are prevalent as a cause and consequence of chronic hepatitis B and C virus infections, alcoholic hepatitis, and non-alcoholic fatty liver disease and steatohepatitis. Recent developments in lipidomics have also revealed that dynamic changes in triacylglycerols, phospholipids, sphingolipids, ceramides, fatty acids, and cholesterol are involved in the development and progression of primary liver cancer. Accordingly, the transcriptional landscape of lipid metabolism suggests a carcinogenic role of increasing fatty acids and sterol synthesis. However, limited mechanistic insights into the complex nature of the hepatic lipidome have so far hindered the development of effective therapies.
Keywords: ACC, acetyl-CoA carboxylase; ACLY, ATP citrate lyase; ALD, alcohol-related liver disease; BAs, bile acids; CCA, cholangiocarcinoma; CPT, carnitine palmitoyltransferase; Cer, ceramide(s); DNL, de novo lipogenesis; ELOV1-6, elongation of very-long-chain fatty acids; FA, fatty acid; FABP, fatty acid-binding protein; FADS2, fatty acid desaturase 2; FAO, fatty acid oxidation; FASN, fatty acid synthase; FXR, farnesoid X receptor; HCC, hepatocellular carcinoma; HMGCR, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase; HSCs, hepatic stellate cells; LA, linoleic acid; LPC, lysophosphatidylcholine; LXR, liver X receptor; MUFA, monounsaturated fatty acid; NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis; Non-alcoholic fatty liver disease; PC, phosphatidylcholine; PPARs, peroxisome proliferator-activated receptors; PSC, primary sclerosing cholangitis; PUFA, polyunsaturated fatty acid; S1P, sphingosine-1-phosphate; SCD, stearoyl-CoA desaturase; SE, sterol esters; SFA, saturated fatty acid; SM, sphingomyelin; SREBP, sterol regulatory element-binding protein; TERT, telomerase reverse transcriptase; TG, triglycerides; TLR, Toll-like receptor; cholangiocarcinoma; hepatocellular carcinoma; lipidomics; metabolomics.
© 2022 The Author(s).