Fatty Acid Metabolism and Acyl-CoA Synthetases in the

Overview

Journal World J Hepatol

Publisher Baishideng Publishing Group

Specialty Gastroenterology

Date 2021 Dec 14

PMID 34904027

Citations 10

Authors

Yunxia Ma

Miljana Nenkov

Yuan Chen

Adrian T Press

Elke Kaemmerer

Nikolaus Gassler

Affiliations

Soon will be listed here.

Abstract

Fatty acids are energy substrates and cell components which participate in regulating signal transduction, transcription factor activity and secretion of bioactive lipid mediators. The acyl-CoA synthetases (ACSs) family containing 26 family members exhibits tissue-specific distribution, distinct fatty acid substrate preferences and diverse biological functions. Increasing evidence indicates that dysregulation of fatty acid metabolism in the , designated as the bidirectional relationship between the gut, microbiome and liver, is closely associated with a range of human diseases including metabolic disorders, inflammatory disease and carcinoma in the gastrointestinal tract and liver. In this review, we depict the role of ACSs in fatty acid metabolism, possible molecular mechanisms through which they exert functions, and their involvement in hepatocellular and colorectal carcinoma, with particular attention paid to long-chain fatty acids and small-chain fatty acids. Additionally, the communication and the liver and gut intersection with the microbiome as well as diseases related to microbiota imbalance in the are addressed. Moreover, the development of potentially therapeutic small molecules, proteins and compounds targeting ACSs in cancer treatment is summarized.

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References

Sakakibara I, Fujino T, Ishii M, Tanaka T, Shimosawa T, Miura S . Fasting-induced hypothermia and reduced energy production in mice lacking acetyl-CoA synthetase 2. Cell Metab. 2009; 9(2):191-202. DOI: 10.1016/j.cmet.2008.12.008. View

Warburg O, Wind F, Negelein E . THE METABOLISM OF TUMORS IN THE BODY. J Gen Physiol. 2009; 8(6):519-30. PMC: 2140820. DOI: 10.1085/jgp.8.6.519. View

Chiang J . Bile acid metabolism and signaling. Compr Physiol. 2013; 3(3):1191-212. PMC: 4422175. DOI: 10.1002/cphy.c120023. View

Veglia F, Tyurin V, Blasi M, De Leo A, Kossenkov A, Donthireddy L . Fatty acid transport protein 2 reprograms neutrophils in cancer. Nature. 2019; 569(7754):73-78. PMC: 6557120. DOI: 10.1038/s41586-019-1118-2. View

Kamp F, Hamilton J . How fatty acids of different chain length enter and leave cells by free diffusion. Prostaglandins Leukot Essent Fatty Acids. 2006; 75(3):149-59. DOI: 10.1016/j.plefa.2006.05.003. View

Murata M, Peranen J, Schreiner R, Wieland F, Kurzchalia T, Simons K . VIP21/caveolin is a cholesterol-binding protein. Proc Natl Acad Sci U S A. 1995; 92(22):10339-43. PMC: 40792. DOI: 10.1073/pnas.92.22.10339. View

Tomoda H, Igarashi K, Omura S . Inhibition of acyl-CoA synthetase by triacsins. Biochim Biophys Acta. 1987; 921(3):595-8. View

Arias-Barrau E, DiRusso C, Black P . Methods to monitor Fatty Acid transport proceeding through vectorial acylation. Methods Mol Biol. 2009; 580:233-49. DOI: 10.1007/978-1-60761-325-1_13. View

Gharib E, Nasrabadi P, Zali M . miR-497-5p mediates starvation-induced death in colon cancer cells by targeting acyl-CoA synthetase-5 and modulation of lipid metabolism. J Cell Physiol. 2020; 235(7-8):5570-5589. DOI: 10.1002/jcp.29488. View

10.

Milligan G, Stoddart L, Smith N . Agonism and allosterism: the pharmacology of the free fatty acid receptors FFA2 and FFA3. Br J Pharmacol. 2009; 158(1):146-53. PMC: 2795255. DOI: 10.1111/j.1476-5381.2009.00421.x. View

11.

Ehmann D, Wendler J, Koeninger L, Larsen I, Klag T, Berger J . Paneth cell α-defensins HD-5 and HD-6 display differential degradation into active antimicrobial fragments. Proc Natl Acad Sci U S A. 2019; 116(9):3746-3751. PMC: 6397583. DOI: 10.1073/pnas.1817376116. View

12.

Blackburn C, Guan B, Brown J, Cullis C, Condon S, Jenkins T . Identification and characterization of 4-aryl-3,4-dihydropyrimidin-2(1H)-ones as inhibitors of the fatty acid transporter FATP4. Bioorg Med Chem Lett. 2006; 16(13):3504-9. DOI: 10.1016/j.bmcl.2006.03.102. View

13.

Wehkamp J, Stange E . Paneth's disease. J Crohns Colitis. 2010; 4(5):523-31. DOI: 10.1016/j.crohns.2010.05.010. View

14.

Van Horn C, Caviglia J, Li L, Wang S, Granger D, Coleman R . Characterization of recombinant long-chain rat acyl-CoA synthetase isoforms 3 and 6: identification of a novel variant of isoform 6. Biochemistry. 2005; 44(5):1635-42. DOI: 10.1021/bi047721l. View

15.

Cui M, Wang Y, Sun B, Xiao Z, Ye L, Zhang X . MiR-205 modulates abnormal lipid metabolism of hepatoma cells via targeting acyl-CoA synthetase long-chain family member 1 (ACSL1) mRNA. Biochem Biophys Res Commun. 2014; 444(2):270-5. DOI: 10.1016/j.bbrc.2014.01.051. View

16.

Chekulayev V, Mado K, Shevchuk I, Koit A, Kaldma A, Klepinin A . Metabolic remodeling in human colorectal cancer and surrounding tissues: alterations in regulation of mitochondrial respiration and metabolic fluxes. Biochem Biophys Rep. 2017; 4:111-125. PMC: 5668899. DOI: 10.1016/j.bbrep.2015.08.020. View

17.

Rios-Covian D, Salazar N, Gueimonde M, de Los Reyes-Gavilan C . Shaping the Metabolism of Intestinal Population through Diet to Improve Human Health. Front Microbiol. 2017; 8:376. PMC: 5339271. DOI: 10.3389/fmicb.2017.00376. View

18.

Hubbard B, Doege H, Punreddy S, Wu H, Huang X, Kaushik V . Mice deleted for fatty acid transport protein 5 have defective bile acid conjugation and are protected from obesity. Gastroenterology. 2006; 130(4):1259-69. DOI: 10.1053/j.gastro.2006.02.012. View

19.

Pakiet A, Kobiela J, Stepnowski P, Sledzinski T, Mika A . Changes in lipids composition and metabolism in colorectal cancer: a review. Lipids Health Dis. 2019; 18(1):29. PMC: 6347819. DOI: 10.1186/s12944-019-0977-8. View

20.

Jahnel J, Fickert P, Hauer A, Hogenauer C, Avian A, Trauner M . Inflammatory bowel disease alters intestinal bile acid transporter expression. Drug Metab Dispos. 2014; 42(9):1423-31. DOI: 10.1124/dmd.114.058065. View