Long-chain acyl-CoA synthetase in fatty acid metabolism involved in liver and other diseases: An update

Abstract

Long-chain acyl-CoA synthetase (ACSL) family members include five different ACSL isoforms, each encoded by a separate gene and have multiple spliced variants. ACSLs on endoplasmic reticulum and mitochondrial outer membrance catalyze fatty acids with chain lengths from 12 to 20 carbon atoms to form acyl-CoAs, which are lipid metabolic intermediates and involved in fatty acid metabolism, membrane modifications and various physiological processes. Gain- or loss-of-function studies have shown that the expression of individual ACSL isoforms can alter the distribution and amount of intracellular fatty acids. Changes in the types and amounts of fatty acids, in turn, can alter the expression of intracellular ACSLs. ACSL family members affect not only the proliferation of normal cells, but the proliferation of malignant tumor cells. They also regulate cell apoptosis through different signaling pathways and molecular mechanisms. ACSL members have individual functions in fatty acid metabolism in different types of cells depending on substrate preferences, subcellular location and tissue specificity, thus contributing to liver diseases and metabolic diseases, such as fatty liver disease, obesity, atherosclerosis and diabetes. They are also linked to neurological disorders and other diseases. However, the mechanisms are unclear. This review addresses new findings in the classification and properties of ACSLs and the fatty acid metabolism-associated effects of ACSLs in diseases.

CDCP1 drives triple-negative breast cancer metastasis through reduction of lipid-droplet abundance and stimulation of fatty acid oxidation

“…This finding is highlighted by a study that found that the pan-ACSL inhibitor, Triacsin C, preferentially inhibited TAG synthesis and did not affect FAO (71). Furthermore, although both ACSL1 and ACSL5 have been reported to localize at the mitochondrial and the LD membranes (72) and ACSL1 has been reported to up-regulate genes involved in FAO (73), they do not affect the FAO rate (74,75). Based on our data, ACSLs promote lipid storage in LDs (Fig.…”

Inhibitory Effect of Oleic Acid on Octanoylated Ghrelin Production

“…Acyl-CoA synthetases are classified based on the carbon chain length of their preferred acyl group. Octanoic acid C8 is the substrate for medium-chain acyl-CoA synthetase ACSM , and 18 carbon length fatty acids such as stearic acid, oleic acid, linoleic acid, and α-linolenic acid, are substrates for long-chain acyl-CoA synthetase 35,36 .…”

Long‐chain acyl‐CoA synthetase 6 regulates lipid synthesis and mitochondrial oxidative capacity in human and rat skeletal muscle

“…Dysfunction of these enzymes can lead to many metabolic diseases, such as those related to metabolic syndrome, fatty liver and neurological disorders (Yan et al . ). In humans, a defect in the activation of the fatty acids by ACSL in the muscle of black women may contribute to the maintenance of obesity (Privette et al .…”