Since the 1950s, one of the goals of adipose tissue research has been to determine lipolytic and lipogenic activity as the primary metabolic pathways affecting adipocyte health and size and thus representing potential therapeutic targets for the treatment of obesity and associated diseases. Nowadays, there is a relatively large number of methods to measure the activity of these pathways and involved enzymes, but their applicability to different biological samples is variable. Here, we review the characteristics of mean lipogenic and lipolytic enzymes, their inhibitors, and available methodologies for assessing their activity, and comment on the advantages and disadvantages of these methodologies and their applicability in vivo, ex vivo, and in vitro, i.e., in cells, organs and their respective extracts, with the emphasis on adipocytes and adipose tissue.

Department of Pathophysiology Center for Research on Nutrition Metabolism and Diabetes 3rd Faculty of Medicine Charles University 100 00 Prague Czech Republic

Franco Czech Laboratory for Clinical Research of Obesity 3rd Faculty of Medicine Charles University 100 00 Prague Czech Republic

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Nye C., Kim J., Kalhan S.C., Hanson R.W. Reassessing triglyceride synthesis in adipose tissue. Trends Endocrinol. Metab. 2008;19:356–361. doi: 10.1016/j.tem.2008.08.003. PubMed DOI

Ahmadian M., Duncan R.E., Jaworski K., Sarkadi-Nagy E. Triacylglycerol metabolism in adipose tissue. Future Lipidol. 2007;2:229–237. doi: 10.2217/17460875.2.2.229. PubMed DOI PMC

Kershaw E.E., Hamm J.K., Verhagen L.A., Peroni O., Katic M., Flier J.S. Adipose triglyceride lipase: Function, regulation by insulin, and comparison with adiponutrin. Diabetes. 2006;55:148–157. doi: 10.2337/diabetes.55.01.06.db05-0982. PubMed DOI PMC

Coppack S.W., Jensen M.D., Miles J.M. In vivo regulation of lipolysis in humans. J. Lipid Res. 1994;35:177–193. doi: 10.1016/S0022-2275(20)41207-6. PubMed DOI

Lafontan M., Langin D. Lipolysis and lipid mobilization in human adipose tissue. Prog. Lipid Res. 2009;48:275–297. doi: 10.1016/j.plipres.2009.05.001. PubMed DOI

Hellerstein M.K. De novo lipogenesis in humans: Metabolic and regulatory aspects. Eur. J. Clin. Nutr. 1999;53((Suppl. 1)):S53–S65. doi: 10.1038/sj.ejcn.1600744. PubMed DOI

Edens N.K., Leibel R.L., Hirsch J. Mechanism of free fatty acid re-esterification in human adipocytes in vitro. J. Lipid Res. 1990;31:1423–1431. doi: 10.1016/S0022-2275(20)42613-6. PubMed DOI

Yen C.-L.E., Stone S.J., Koliwad S., Harris C., Farese R.V. Thematic Review Series: Glycerolipids. DGAT enzymes and triacylglycerol biosynthesis. J. Lipid Res. 2008;49:2283–2301. doi: 10.1194/jlr.R800018-JLR200. PubMed DOI PMC

Ameer F., Scandiuzzi L., Hasnain S., Kalbacher H., Zaidi N. De novo lipogenesis in health and disease. Metabolism. 2014;63:895–902. doi: 10.1016/j.metabol.2014.04.003. PubMed DOI

Morigny P., Boucher J., Arner P., Langin D. Lipid and glucose metabolism in white adipocytes: Pathways, dysfunction and therapeutics. Nat. Rev. Endocrinol. 2021;17:276–295. doi: 10.1038/s41574-021-00471-8. PubMed DOI

Morigny P., Houssier M., Mouisel E., Langin D. Adipocyte lipolysis and insulin resistance. Biochimie. 2016;125:259–266. doi: 10.1016/j.biochi.2015.10.024. PubMed DOI

van Herpen N.A., Schrauwen-Hinderling V.B. Lipid accumulation in non-adipose tissue and lipotoxicity. Physiol. Behav. 2008;94:231–241. doi: 10.1016/j.physbeh.2007.11.049. PubMed DOI

Schaffer J.E. Lipotoxicity: When tissues overeat. Curr. Opin. Lipidol. 2003;14:281–287. doi: 10.1097/00041433-200306000-00008. PubMed DOI

Savage D.B., Petersen K.F., Shulman G.I. Disordered lipid metabolism and the pathogenesis of insulin resistance. Physiol. Rev. 2007;87:507–520. doi: 10.1152/physrev.00024.2006. PubMed DOI PMC

Balkau B., Valensi P., Eschwege E., Slama G. A review of the metabolic syndrome. Diabetes Metab. 2007;33:405–413. doi: 10.1016/j.diabet.2007.08.001. PubMed DOI

Qureshi K., Abrams G.A. Metabolic liver disease of obesity and role of adipose tissue in the pathogenesis of nonalcoholic fatty liver disease. World J. Gastroenterol. 2007;13:3540–3553. doi: 10.3748/wjg.v13.i26.3540. PubMed DOI PMC

DeFronzo R.A. Pathogenesis of type 2 diabetes mellitus. Med. Clin. N. Am. 2004;88:787–835. doi: 10.1016/j.mcna.2004.04.013. PubMed DOI

Baracos V.E., Martin L., Korc M., Guttridge D.C., Fearon K.C.H. Cancer-associated cachexia. Nat. Rev. Dis. Primers. 2018;4:17105. doi: 10.1038/nrdp.2017.105. PubMed DOI

Smith G.I., Shankaran M., Yoshino M., Schweitzer G.G., Chondronikola M., Beals J.W., Okunade A.L., Patterson B.W., Nyangau E., Field T., et al. Insulin resistance drives hepatic de novo lipogenesis in nonalcoholic fatty liver disease. J. Clin. Investig. 2020;130:1453–1460. doi: 10.1172/JCI134165. PubMed DOI PMC

Yilmaz M., Claiborn K.C., Hotamisligil G.S. De Novo Lipogenesis Products and Endogenous Lipokines. Diabetes. 2016;65:1800–1807. doi: 10.2337/db16-0251. PubMed DOI PMC

Song Z., Xiaoli A.M., Yang F. Regulation and Metabolic Significance of De Novo Lipogenesis in Adipose Tissues. Nutrients. 2018;10:1383. doi: 10.3390/nu10101383. PubMed DOI PMC

Scheja L., Heeren J. The endocrine function of adipose tissues in health and cardiometabolic disease. Nat. Rev. Endocrinol. 2019;15:507–524. doi: 10.1038/s41574-019-0230-6. PubMed DOI

Long J.Z., Cravatt B.F. The metabolic serine hydrolases and their functions in mammalian physiology and disease. Chem. Rev. 2011;111:6022–6063. doi: 10.1021/cr200075y. PubMed DOI PMC

Karlsson M., Contreras J.A., Hellman U., Tornqvist H., Holm C. cDNA cloning, tissue distribution, and identification of the catalytic triad of monoglyceride lipase. Evolutionary relationship to esterases, lysophospholipases, and haloperoxidases. J. Biol. Chem. 1997;272:27218–27223. doi: 10.1074/jbc.272.43.27218. PubMed DOI

Long J.Z., Nomura D.K., Cravatt B.F. Characterization of monoacylglycerol lipase inhibition reveals differences in central and peripheral endocannabinoid metabolism. Chem. Biol. 2009;16:744–753. doi: 10.1016/j.chembiol.2009.05.009. PubMed DOI PMC

Gamblin C., Rouault C., Lacombe A., Langa-Vives F., Farabos D., Lamaziere A., Clement K., Gautier E.L., Yvan-Charvet L., Dugail I. Lysosomal Acid Lipase Drives Adipocyte Cholesterol Homeostasis and Modulates Lipid Storage in Obesity, Independent of Autophagy. Diabetes. 2021;70:76–90. doi: 10.2337/db20-0578. PubMed DOI

Zechner R., Kienesberger P.C., Haemmerle G., Zimmermann R., Lass A. Adipose triglyceride lipase and the lipolytic catabolism of cellular fat stores. J. Lipid Res. 2009;50:3–21. doi: 10.1194/jlr.R800031-JLR200. PubMed DOI

Zimmermann R., Strauss J.G., Haemmerle G., Schoiswohl G., Birner-Gruenberger R., Riederer M., Lass A., Neuberger G., Eisenhaber F., Hermetter A., et al. Fat Mobilization in Adipose Tissue is Promoted by Adopose Triglyceride Lipase. Science. 2004;306:1383–1386. doi: 10.1126/science.1100747. PubMed DOI

Zimmermann R., Lass A., Haemmerle G., Zechner R. Fate of fat: The role of adipose triglyceride lipase in lipolysis. Biochim. Biophys. Acta. 2009;1791:494–500. doi: 10.1016/j.bbalip.2008.10.005. PubMed DOI

Obrowsky S., Chandak P.G., Patankar J.V., Povoden S., Schlager S., Kershaw E.E., Bogner-Strauss J.G., Hoefler G., Levak-Frank S., Kratky D. Adipose triglyceride lipase is a TG hydrolase of the small intestine and regulates intestinal PPARalpha signaling. J. Lipid Res. 2013;54:425–435. doi: 10.1194/jlr.M031716. PubMed DOI PMC

Liu S., Promes J.A., Harata M., Mishra A., Stephens S.B., Taylor E.B., Burand A.J., Jr., Sivitz W.I., Fink B.D., Ankrum J.A., et al. Adipose Triglyceride Lipase Is a Key Lipase for the Mobilization of Lipid Droplets in Human beta-Cells and Critical for the Maintenance of Syntaxin 1a Levels in beta-Cells. Diabetes. 2020;69:1178–1192. doi: 10.2337/db19-0951. PubMed DOI PMC

Cerk I.K., Wechselberger L., Oberer M. Adipose Triglyceride Lipase Regulation: An Overview. Curr. Protein Pept. Sci. 2018;19:221–233. doi: 10.2174/1389203718666170918160110. PubMed DOI PMC

Lass A., Zimmermann R., Haemmerle G., Riederer M., Schoiswohl G., Schweiger M., Kienesberger P., Strauss J.G., Gorkiewicz G., Zechner R. Adipose triglyceride lipase-mediated lipolysis of cellular fat stores is activated by CGI-58 and defective in Chanarin-Dorfman Syndrome. Cell Metab. 2006;3:309–319. doi: 10.1016/j.cmet.2006.03.005. PubMed DOI

Kimmel A.R., Sztalryd C. The Perilipins: Major Cytosolic Lipid Droplet-Associated Proteins and Their Roles in Cellular Lipid Storage, Mobilization, and Systemic Homeostasis. Annu. Rev. Nutr. 2016;36:471–509. doi: 10.1146/annurev-nutr-071813-105410. PubMed DOI

Granneman J.G., Moore H.P., Mottillo E.P., Zhu Z., Zhou L. Interactions of perilipin-5 (Plin5) with adipose triglyceride lipase. J. Biol. Chem. 2011;286:5126–5135. doi: 10.1074/jbc.M110.180711. PubMed DOI PMC

Sztalryd C., Brasaemle D.L. The perilipin family of lipid droplet proteins: Gatekeepers of intracellular lipolysis. Biochim. Biophys. Acta Mol. Cell Biol. Lipids. 2017;1862:1221–1232. doi: 10.1016/j.bbalip.2017.07.009. PubMed DOI PMC

Yang X., Lu X., Lombes M., Rha G.B., Chi Y.I., Guerin T.M., Smart E.J., Liu J. The G(0)/G(1) switch gene 2 regulates adipose lipolysis through association with adipose triglyceride lipase. Cell Metab. 2010;11:194–205. doi: 10.1016/j.cmet.2010.02.003. PubMed DOI PMC

Nagy H.M., Paar M., Heier C., Moustafa T., Hofer P., Haemmerle G., Lass A., Zechner R., Oberer M., Zimmermann R. Adipose triglyceride lipase activity is inhibited by long-chain acyl-coenzyme A. Biochim. Biophys. Acta. 2014;1841:588–594. doi: 10.1016/j.bbalip.2014.01.005. PubMed DOI PMC

Mayer N., Schweiger M., Romauch M., Grabner G.F., Eichmann T.O., Fuchs E., Ivkovic J., Heier C., Mrak I., Lass A., et al. Development of small-molecule inhibitors targeting adipose triglyceride lipase. Nat. Chem. Biol. 2013;9:785–787. doi: 10.1038/nchembio.1359. PubMed DOI PMC

Iglesias J., Lamontagne J., Erb H., Gezzar S., Zhao S., Joly E., Truong V.L., Skorey K., Crane S., Madiraju S.R., et al. Simplified assays of lipolysis enzymes for drug discovery and specificity assessment of known inhibitors. J. Lipid Res. 2016;57:131–141. doi: 10.1194/jlr.D058438. PubMed DOI PMC

Grabner G.F., Guttenberger N., Mayer N., Migglautsch-Sulzer A.K., Lembacher-Fadum C., Fawzy N., Bulfon D., Hofer P., Zullig T., Hartig L., et al. Small-Molecule Inhibitors Targeting Lipolysis in Human Adipocytes. J. Am. Chem. Soc. 2022;144:6237–6250. doi: 10.1021/jacs.1c10836. PubMed DOI PMC

Reisenberg M., Singh P.K., Williams G., Doherty P. The diacylglycerol lipases: Structure, regulation and roles in and beyond endocannabinoid signalling. Philos. Trans. R. Soc. Lond. B Biol. Sci. 2012;367:3264–3275. doi: 10.1098/rstb.2011.0387. PubMed DOI PMC

Kridel S.J., Axelrod F., Rozenkrantz N., Smith J.W. Orlistat is a novel inhibitor of fatty acid synthase with antitumor activity. Cancer Res.. 2004;64:2070–2075. doi: 10.1158/0008-5472.CAN-03-3645. PubMed DOI

McNeely W., Benfield P. Orlistat. Drugs. 1998;56:241–249. doi: 10.2165/00003495-199856020-00007. discussion 250. PubMed DOI

Sjöström L., Rissanen A., Andersen T., Boldrin M., Golay A., Koppeschaar H.P.F., Krempf M. Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. Lancet. 1998;352:167–172. doi: 10.1016/S0140-6736(97)11509-4. PubMed DOI

Ballinger A., Peikin S.R. Orlistat: Its current status as an anti-obesity drug. Eur. J. Pharmacol. 2001;440:109–117. doi: 10.1016/S0014-2999(02)01422-X. PubMed DOI

Korbelius M., Vujic N., Sachdev V., Obrowsky S., Rainer S., Gottschalk B., Graier W.F., Kratky D. ATGL/CGI-58-Dependent Hydrolysis of a Lipid Storage Pool in Murine Enterocytes. Cell Rep. 2019;28:1923–1934.e4. doi: 10.1016/j.celrep.2019.07.030. PubMed DOI PMC

Cornaciu I., Boeszoermenyi A., Lindermuth H., Nagy H.M., Cerk I.K., Ebner C., Salzburger B., Gruber A., Schweiger M., Zechner R., et al. The minimal domain of adipose triglyceride lipase (ATGL) ranges until leucine 254 and can be activated and inhibited by CGI-58 and G0S2, respectively. PLoS ONE. 2011;6:e26349. doi: 10.1371/journal.pone.0026349. PubMed DOI PMC

Filleur S., Nelius T., de Riese W., Kennedy R.C. Characterization of PEDF: A multi-functional serpin family protein. J. Cell. Biochem. 2009;106:769–775. doi: 10.1002/jcb.22072. PubMed DOI

Chen Y., Carlessi R., Walz N., Cruzat V.F., Keane K., John A.N., Jiang F.X., Carnagarin R., Dass C.R., Newsholme P. Pigment epithelium-derived factor (PEDF) regulates metabolism and insulin secretion from a clonal rat pancreatic beta cell line BRIN-BD11 and mouse islets. Mol. Cell. Endocrinol. 2016;426:50–60. doi: 10.1016/j.mce.2016.02.004. PubMed DOI

Kulminskaya N., Oberer M. Protein-protein interactions regulate the activity of Adipose Triglyceride Lipase in intracellular lipolysis. Biochimie. 2020;169:62–68. doi: 10.1016/j.biochi.2019.08.004. PubMed DOI

Kimmel A.R., Sztalryd C. Perilipin 5, a lipid droplet protein adapted to mitochondrial energy utilization. Curr. Opin. Lipidol. 2014;25:110–117. doi: 10.1097/MOL.0000000000000057. PubMed DOI PMC

Zagani R., El-Assaad W., Gamache I., Teodoro J.G. Inhibition of adipose triglyceride lipase (ATGL) by the putative tumor suppressor G0S2 or a small molecule inhibitor attenuates the growth of cancer cells. Oncotarget. 2015;6:28282–28295. doi: 10.18632/oncotarget.5061. PubMed DOI PMC

Wan Z., Matravadia S., Holloway G.P., Wright D.C. FAT/CD36 regulates PEPCK expression in adipose tissue. Am. J. Physiol. Cell Physiol. 2013;304:C478–C484. doi: 10.1152/ajpcell.00372.2012. PubMed DOI

de Oliveira C., Khatua B., Noel P., Kostenko S., Bag A., Balakrishnan B., Patel K.S., Guerra A.A., Martinez M.N., Trivedi S., et al. Pancreatic triglyceride lipase mediates lipotoxic systemic inflammation. J. Clin. Investig. 2020;130:1931–1947. doi: 10.1172/JCI132767. PubMed DOI PMC

Fako V.E., Zhang J.T., Liu J.Y. Mechanism of Orlistat Hydrolysis by the Thioesterase of Human Fatty Acid Synthase. ACS Catal. 2014;4:3444–3453. doi: 10.1021/cs500956m. PubMed DOI PMC

Yeaman S.J. Hormone-sensitive lipase--new roles for an old enzyme. Biochem. J. 2004;379:11–22. doi: 10.1042/bj20031811. PubMed DOI PMC

Mita T., Furuhashi M., Hiramitsu S., Ishii J., Hoshina K., Ishimura S., Fuseya T., Watanabe Y., Tanaka M., Ohno K., et al. FABP4 is secreted from adipocytes by adenyl cyclase-PKA- and guanylyl cyclase-PKG-dependent lipolytic mechanisms. Obesity. 2015;23:359–367. doi: 10.1002/oby.20954. PubMed DOI

Holm C. Molecular mechanisms regulating hormone-sensitive lipase and lipolysis. Biochem. Soc. Trans. 2003;31:1120–1124. doi: 10.1042/bst0311120. PubMed DOI

Watt M.J., Holmes A.G., Pinnamaneni S.K., Garnham A.P., Steinberg G.R., Kemp B.E., Febbraio M.A. Regulation of HSL serine phosphorylation in skeletal muscle and adipose tissue. Am. J. Physiol. Endocrinol. Metab. 2006;290:E500–E508. doi: 10.1152/ajpendo.00361.2005. PubMed DOI

Viollet B., Andreelli F., Jorgensen S.B., Perrin C., Flamez D., Mu J., Wojtaszewski J.F., Schuit F.C., Birnbaum M., Richter E., et al. Physiological role of AMP-activated protein kinase (AMPK): Insights from knockout mouse models. Biochem. Soc. Trans. 2003;31:216–219. doi: 10.1042/bst0310216. PubMed DOI

Ueno M., Suzuki J., Hirose M., Sato S., Imagawa M., Zenimaru Y., Takahashi S., Ikuyama S., Koizumi T., Konoshita T., et al. Cardiac overexpression of perilipin 2 induces dynamic steatosis: Prevention by hormone-sensitive lipase. Am. J. Physiol. Endocrinol. Metab. 2017;313:E699–E709. doi: 10.1152/ajpendo.00098.2017. PubMed DOI PMC

Claus T.H., Lowe D.B., Liang Y., Salhanick A.I., Lubeski C.K., Yang L., Lemoine L., Zhu J., Clairmont K.B. Specific inhibition of hormone-sensitive lipase improves lipid profile while reducing plasma glucose. J. Pharmacol. Exp. Ther. 2005;315:1396–1402. doi: 10.1124/jpet.105.086926. PubMed DOI

Mottillo E.P., Shen X.J., Granneman J.G. Role of hormone-sensitive lipase in beta-adrenergic remodeling of white adipose tissue. Am. J. Physiol. Endocrinol. Metab. 2007;293:E1188–E1197. doi: 10.1152/ajpendo.00051.2007. PubMed DOI

Gao H., Feng X.J., Li Z.M., Li M., Gao S., He Y.H., Wang J.J., Zeng S.Y., Liu X.P., Huang X.Y., et al. Downregulation of adipose triglyceride lipase promotes cardiomyocyte hypertrophy by triggering the accumulation of ceramides. Arch Biochem. Biophys. 2015;565:76–88. doi: 10.1016/j.abb.2014.11.009. PubMed DOI

Ebdrup ø., Refsgaard H.H.F., Fledelius C., Jacobsen P. Synthesis and Structure-Activity Relationship for a Novel Class of Potent and Selective Carbamate-Based Inhibitors of Hormone Selective Lipase with Acute In Vivo Antilipolytic Effects. J. Med. Chem. 2006;2007:5449–5456. doi: 10.1021/jm0607653. PubMed DOI

Bustanji Y., Issa A., Mohammad M., Hudaib M., Tawah K., Alkhatib H., Almasri I., Al-Khalidi B. Inhibition of hormone sensitive lipase and pancreatic lipase by Rosmarinus officinalis extract and selected phenolic constituents. J. Med. Plants Res. 2010;4:2235–2242. doi: 10.5897/JMPR10.399. DOI

Vagelos P.R., Alberts A.W., Martin D.B. Studies on the Mechanism of Activation of Acetyl Coenzyme A Carboxylase by Citrate. J. Biol. Chem. 1963;238:533–540. doi: 10.1016/S0021-9258(18)81295-9. PubMed DOI

Beaty N.B., Lane M.D. Kinetics of activation of acetyl-CoA carboxylase by citrate. Relationship to the rate of polymerization of the enzyme. J. Biol. Chem. 1983;258:13043–13050. doi: 10.1016/S0021-9258(17)44077-4. PubMed DOI

Hardie D.G., Cohen P. Purification and physicochemical properties of fatty acid synthetase and acetyl-CoA carboxylase from lactating rabbit mammary gland. Eur. J. Biochem. 1978;92:25–34. doi: 10.1111/j.1432-1033.1978.tb12719.x. PubMed DOI

Boone A.N., Chan A., Kulpa J.E., Brownsey R.W. Bimodal activation of acetyl-CoA carboxylase by glutamate. J. Biol. Chem. 2000;275:10819–10825. doi: 10.1074/jbc.275.15.10819. PubMed DOI

Kowluru A., Chen H.-Q., Modrick L.M., Stefanelli C. Activation of Acetyl-CoA Carboxylase by a Glutamateand Magnesium-Sensitive Protein Phosphatase in the Islet β-Cell. Diabetes. 2001;50:1580–1587. doi: 10.2337/diabetes.50.7.1580. PubMed DOI

Brownsey R.W., Boone A.N., Elliott J.E., Kulpa J.E., Lee W.M. Regulation of acetyl-CoA carboxylase. Biochem. Soc. Trans. 2006;34:223–227. doi: 10.1042/BST0340223. PubMed DOI

Galic S., Loh K., Murray-Segal L., Steinberg G.R., Andrews Z.B., Kemp B.E. AMPK signaling to acetyl-CoA carboxylase is required for fasting- and cold-induced appetite but not thermogenesis. Elife. 2018;7:e32656. doi: 10.7554/eLife.32656. PubMed DOI PMC

Levert K.L., Waldrop G.L., Stephens J.M. A biotin analog inhibits acetyl-CoA carboxylase activity and adipogenesis. J. Biol. Chem. 2002;277:16347–16350. doi: 10.1074/jbc.C200113200. PubMed DOI

Munday M.R. Regulation of mammalian acetyl-CoA carboxylase. Biochem. Soc. Trans. 2002;30:1059–1064. doi: 10.1042/bst0301059. PubMed DOI

Harwood H.J., Jr., Petras S.F., Shelly L.D., Zaccaro L.M., Perry D.A., Makowski M.R., Hargrove D.M., Martin K.A., Tracey W.R., Chapman J.G., et al. Isozyme-nonselective N-substituted bipiperidylcarboxamide acetyl-CoA carboxylase inhibitors reduce tissue malonyl-CoA concentrations, inhibit fatty acid synthesis, and increase fatty acid oxidation in cultured cells and in experimental animals. J. Biol. Chem. 2003;278:37099–37111. doi: 10.1074/jbc.M304481200. PubMed DOI

Chen L., Duan Y., Wei H., Ning H., Bi C., Zhao Y., Qin Y., Li Y. Acetyl-CoA carboxylase (ACC) as a therapeutic target for metabolic syndrome and recent developments in ACC1/2 inhibitors. Expert Opin. Investig. Drugs. 2019;28:917–930. doi: 10.1080/13543784.2019.1657825. PubMed DOI

Gerth K., Bedorf N., Irschik H., Hofle G., Reichenbach H. The soraphens: A family of novel antifungal compounds from Sorangium cellulosum (Myxobacteria). I. Soraphen A1 alpha: Fermentation, isolation, biological properties. J. Antibiot. 1994;47:23–31. doi: 10.7164/antibiotics.47.23. PubMed DOI

Schreurs M., van Dijk T.H., Gerding A., Havinga R., Reijngoud D.J., Kuipers F. Soraphen, an inhibitor of the acetyl-CoA carboxylase system, improves peripheral insulin sensitivity in mice fed a high-fat diet. Diabetes Obes. Metab. 2009;11:987–991. doi: 10.1111/j.1463-1326.2009.01078.x. PubMed DOI

Jump D.B., Torres-Gonzalez M., Olson L.K. Soraphen A, an inhibitor of acetyl CoA carboxylase activity, interferes with fatty acid elongation. Biochem. Pharmacol. 2011;81:649–660. doi: 10.1016/j.bcp.2010.12.014. PubMed DOI PMC

Harwood H.J., Jr. Treating the metabolic syndrome: Acetyl-CoA carboxylase inhibition. Expert Opin. Ther. Targets. 2005;9:267–281. doi: 10.1517/14728222.9.2.267. PubMed DOI

Beckers A., Organe S., Timmermans L., Scheys K., Peeters A., Brusselmans K., Verhoeven G., Swinnen J.V. Chemical inhibition of acetyl-CoA carboxylase induces growth arrest and cytotoxicity selectively in cancer cells. Cancer Res. 2007;67:8180–8187. doi: 10.1158/0008-5472.CAN-07-0389. PubMed DOI

Harriman G., Greenwood J., Bhat S., Huang X., Wang R., Paul D., Tong L., Saha A.K., Westlin W.F., Kapeller R., et al. Acetyl-CoA carboxylase inhibition by ND-630 reduces hepatic steatosis, improves insulin sensitivity, and modulates dyslipidemia in rats. Proc. Natl. Acad. Sci. USA. 2016;113:E1796–E1805. doi: 10.1073/pnas.1520686113. PubMed DOI PMC

Li E.Q., Zhao W., Zhang C., Qin L.Z., Liu S.J., Feng Z.Q., Wen X., Chen C.P. Synthesis and anti-cancer activity of ND-646 and its derivatives as acetyl-CoA carboxylase 1 inhibitors. Eur. J. Pharm. Sci. 2019;137:105010. doi: 10.1016/j.ejps.2019.105010. PubMed DOI

Svensson R.U., Parker S.J., Eichner L.J., Kolar M.J., Wallace M., Brun S.N., Lombardo P.S., Van Nostrand J.L., Hutchins A., Vera L., et al. Inhibition of acetyl-CoA carboxylase suppresses fatty acid synthesis and tumor growth of non-small-cell lung cancer in preclinical models. Nat. Med. 2016;22:1108–1119. doi: 10.1038/nm.4181. PubMed DOI PMC

Bourbeau M.P., Bartberger M.D. Recent advances in the development of acetyl-CoA carboxylase (ACC) inhibitors for the treatment of metabolic disease. J. Med. Chem. 2015;58:525–536. doi: 10.1021/jm500695e. PubMed DOI

Esler W.P., Tesz G.J., Hellerstein M.K., Beysen C., Sivamani R., Turner S.M., Watkins S.M., Amor P.A., Carvajal-Gonzalez S., Geoly F.J., et al. Human sebum requires de novo lipogenesis, which is increased in acne vulgaris and suppressed by acetyl-CoA carboxylase inhibition. Sci. Transl. Med. 2019;11:eaau8465. doi: 10.1126/scitranslmed.aau8465. PubMed DOI

Huard K., Smith A.C., Cappon G., Dow R.L., Edmonds D.J., El-Kattan A., Esler W.P., Fernando D.P., Griffith D.A., Kalgutkar A.S., et al. Optimizing the Benefit/Risk of Acetyl-CoA Carboxylase Inhibitors through Liver Targeting. J. Med. Chem. 2020;63:10879–10896. doi: 10.1021/acs.jmedchem.0c00640. PubMed DOI

Ryder T.F., Bergman A., King-Ahmad A., Amin N.B., Lall M.S., Ballard T.E., Kalgutkar A.S. Pharmacokinetics, mass balance, metabolism, and excretion of the liver-targeted acetyl-CoA carboxylase inhibitor PF-05221304 (clesacostat) in humans. Xenobiotica. 2022;52:240–253. doi: 10.1080/00498254.2022.2062487. PubMed DOI

Huang H., McIntosh A.L., Martin G.G., Petrescu A.D., Landrock K.K., Landrock D., Kier A.B., Schroeder F. Inhibitors of Fatty Acid Synthesis Induce PPAR alpha -Regulated Fatty Acid beta -Oxidative Genes: Synergistic Roles of L-FABP and Glucose. PPAR Res. 2013;2013:865604. doi: 10.1155/2013/865604. PubMed DOI PMC

Wang C., Xu C., Sun M., Luo D., Liao D.F., Cao D. Acetyl-CoA carboxylase-alpha inhibitor TOFA induces human cancer cell apoptosis. Biochem. Biophys. Res. Commun. 2009;385:302–306. doi: 10.1016/j.bbrc.2009.05.045. PubMed DOI PMC

Thupari J.N., Pinn M.L., Kuhajda F.P. Fatty acid synthase inhibition in human breast cancer cells leads to malonyl-CoA-induced inhibition of fatty acid oxidation and cytotoxicity. Biochem. Biophys. Res. Commun. 2001;285:217–223. doi: 10.1006/bbrc.2001.5146. PubMed DOI

Kim K.W., Yamane H., Zondlo J., Busby J., Wang M. Expression, purification, and characterization of human acetyl-CoA carboxylase 2. Protein Expr. Purif. 2007;53:16–23. doi: 10.1016/j.pep.2006.11.021. PubMed DOI

Pizer E.S., Jackisch C., Wood F.D., Pasternack G.R., Davidson N.E., Kuhajda F.P. Inhibition of fatty acid synthesis induces programmed cell death in human breast cancer cells. Cancer Res. 1996;56:2745–2747. PubMed

Pizer E.S., Chrest F.J., DiGiuseppe J.A., Han W.F. Pharmacological inhibitors of mammalian fatty acid synthase suppress DNA replication and induce apoptosis in tumor cell lines. Cancer Res. 1998;58:4611–4615. PubMed

Vance D., Omura S., Nomura S., Mitsuhashi O., Bloch K., Goldberg I. Inhibition of Fatty-Acid Synthetases by Antibiotic Cerulenin. Biochem. Biophys. Res. Commun. 1972;48:649–656. doi: 10.1016/0006-291X(72)90397-X. PubMed DOI

Vazquez-Martin A., Ropero S., Brunet J., Colomer R., Menendez J.A. Inhibition of Fatty Acid Synthase (FASN) synergistically enhances the efficacy of 5-fluorouracil in breast carcinoma cells. Oncol. Rep. 2007;18:973–980. doi: 10.3892/or.18.4.973. PubMed DOI

Johansson P., Wiltschi B., Kumari P., Kessler B., Vonrhein C., Vonck J., Oesterhelt D., Grininger M. Inhibition of the fungal fatty acid synthase type I multienzyme complex. Proc. Natl. Acad. Sci. USA. 2008;105:12803–12808. doi: 10.1073/pnas.0805827105. PubMed DOI PMC

Rudolph M.C., Karl Maluf N., Wellberg E.A., Johnson C.A., Murphy R.C., Anderson S.M. Mammalian fatty acid synthase activity from crude tissue lysates tracing (1)(3)C-labeled substrates using gas chromatography-mass spectrometry. Anal. Biochem. 2012;428:158–166. doi: 10.1016/j.ab.2012.06.013. PubMed DOI PMC

Kuhajda F.P., Pizer E.S., Li J.N., Mani N.S., Frehywot G.L., Townsend C.A. Synthesis and antitumor activity of an inhibitor of fatty acid synthase. Proc. Natl. Acad. Sci. USA. 2000;97:3450–3454. doi: 10.1073/pnas.97.7.3450. PubMed DOI PMC

Rendina A.R., Cheng D. Characterization of the inactivation of rat fatty acid synthase by C75: Inhibition of partial reactions and protection by substrates. Biochem. J. 2005;388:895–903. doi: 10.1042/BJ20041963. PubMed DOI PMC

Boelcke W.P., Teixeira I.F., Aquino I.G., Mazzaro A.R., Cuadra-Zelaya F.J.M., de Souza A.P., Salo T., Della Coletta R., Graner E., Bastos D.C. Pharmacological fatty acid synthase inhibitors differently affect the malignant phenotype of oral cancer cells. Arch. Oral Biol. 2022;135:105343. doi: 10.1016/j.archoralbio.2021.105343. PubMed DOI

Liu H., Liu J.-Y., Wu X., Zhang J.-T. Biochemistry, molecular biology, and pharmacology of fatty acid synthase, an emerging therapeutic target and diagnosis/prognosis marke. Int. J. Biochem. Mol. Biol. 2010;1:69–89. PubMed PMC

Pemble C.W.t., Johnson L.C., Kridel S.J., Lowther W.T. Crystal structure of the thioesterase domain of human fatty acid synthase inhibited by Orlistat. Nat. Struct. Mol. Biol. 2007;14:704–709. doi: 10.1038/nsmb1265. PubMed DOI

Zhang J.S., Lei J.P., Wei G.Q., Chen H., Ma C.Y., Jiang H.Z. Natural fatty acid synthase inhibitors as potent therapeutic agents for cancers: A review. Pharm. Biol. 2016;54:1919–1925. doi: 10.3109/13880209.2015.1113995. PubMed DOI

Liu B., Wang Y., Fillgrove K.L., Anderson V.E. Triclosan inhibits enoyl-reductase of type I fatty acid synthase in vitro and is cytotoxic to MCF-7 and SKBr-3 breast cancer cells. Cancer Chemother. Pharmacol. 2002;49:187–193. doi: 10.1007/s00280-001-0399-x. PubMed DOI

Stewart M.J., Parikh S., Xiao G., Tonge P.J., Kisker C. Structural basis and mechanism of enoyl reductase inhibition by triclosan. J. Mol. Biol. 1999;290:859–865. doi: 10.1006/jmbi.1999.2907. PubMed DOI

Sun D., Zhao T., Long K., Wu M., Zhang Z. Triclosan down-regulates fatty acid synthase through microRNAs in HepG2 cells. Eur. J. Pharmacol. 2021;907:174261. doi: 10.1016/j.ejphar.2021.174261. PubMed DOI

Sadowski M.C., Pouwer R.H., Gunter J.H., Lubik A.A., Quinn R.J., Nelson C.C. The fatty acid synthase inhibitor triclosan: Repurposing an antimicrobial agent for targeting prostate cancer. Oncotarget. 2014;5:9362–9381. doi: 10.18632/oncotarget.2433. PubMed DOI PMC

Recazens E., Mouisel E., Langin D. Hormone-sensitive lipase: Sixty years later. Prog. Lipid Res. 2021;82:101084. doi: 10.1016/j.plipres.2020.101084. PubMed DOI

Bezaire V., Mairal A., Anesia R., Lefort C., Langin D. Chronic TNFalpha and cAMP pre-treatment of human adipocytes alter HSL, ATGL and perilipin to regulate basal and stimulated lipolysis. FEBS Lett. 2009;583:3045–3049. doi: 10.1016/j.febslet.2009.08.019. PubMed DOI

Langin D., Dicker A., Tavernier G., Hoffstedt J., Mairal A., Ryden M., Arner E., Sicard A., Jenkins C.M., Viguerie N., et al. Adipocyte lipases and defect of lipolysis in human obesity. Diabetes. 2005;54:3190–3197. doi: 10.2337/diabetes.54.11.3190. PubMed DOI

Agustsson T., Ryden M., Hoffstedt J., van Harmelen V., Dicker A., Laurencikiene J., Isaksson B., Permert J., Arner P. Mechanism of increased lipolysis in cancer cachexia. Cancer Res. 2007;67:5531–5537. doi: 10.1158/0008-5472.CAN-06-4585. PubMed DOI

Kim K., Kang J.K., Jung Y.H., Lee S.B., Rametta R., Dongiovanni P., Valenti L., Pajvani U.B. Adipocyte PHLPP2 inhibition prevents obesity-induced fatty liver. Nat. Commun. 2021;12:1822. doi: 10.1038/s41467-021-22106-2. PubMed DOI PMC

Heier C., Knittelfelder O., Hofbauer H.F., Mende W., Pornbacher I., Schiller L., Schoiswohl G., Xie H., Gronke S., Shevchenko A., et al. Hormone-sensitive lipase couples intergenerational sterol metabolism to reproductive success. Elife. 2021;10:e63252. doi: 10.7554/eLife.63252. PubMed DOI PMC

Shiau M.Y., Chuang P.H., Yang C.P., Hsiao C.W., Chang S.W., Chang K.Y., Liu T.M., Chen H.W., Chuang C.C., Yuan S.Y., et al. Mechanism of Interleukin-4 Reducing Lipid Deposit by Regulating Hormone-Sensitive Lipase. Sci. Rep. 2019;9:11974. doi: 10.1038/s41598-019-47908-9. PubMed DOI PMC

Arredondo-Amador M., Zambrano C., Kulyte A., Lujan J., Hu K., Sanchez de Medina F., Scheer F., Arner P., Ryden M., Martinez-Augustin O., et al. Circadian Rhythms in Hormone-sensitive Lipase in Human Adipose Tissue: Relationship to Meal Timing and Fasting Duration. J. Clin. Endocrinol. Metab. 2020;105:e4407–e4416. doi: 10.1210/clinem/dgaa492. PubMed DOI PMC

Zhuan Q., Ma H., Chen J., Luo Y., Luo Y., Gao L., Hou Y., Zhu S., Fu X. Cytoplasm lipids can be modulated through hormone-sensitive lipase and are related to mitochondrial function in porcine IVM oocytes. Reprod. Fertil. Dev. 2020;32:667–675. doi: 10.1071/RD19047. PubMed DOI

Schweiger M., Eichmann T.O., Taschler U., Zimmermann R., Zechner R., Lass A. Measurement of lipolysis. Methods Enzymol. 2014;538:171–193. doi: 10.1016/B978-0-12-800280-3.00010-4. PubMed DOI PMC

Holm C., Contreras J.A., Verger R., Schotz M.C. Large-scale purification and kinetic properties of recombinant hormone-sensitive lipase from baculovirus-insect cell systems. Methods Enzymol. 1997;284:272–284. doi: 10.1016/s0076-6879(97)84018-9. PubMed DOI

Steinberg G.R., Kemp B.E., Watt M.J. Adipocyte triglyceride lipase expression in human obesity. Am. J. Physiol. Endocrinol. Metab. 2007;293:E958–E964. doi: 10.1152/ajpendo.00235.2007. PubMed DOI

Schweiger M., Schreiber R., Haemmerle G., Lass A., Fledelius C., Jacobsen P., Tornqvist H., Zechner R., Zimmermann R. Adipose triglyceride lipase and hormone-sensitive lipase are the major enzymes in adipose tissue triacylglycerol catabolism. J. Biol. Chem. 2006;281:40236–40241. doi: 10.1074/jbc.M608048200. PubMed DOI

Haemmerle G., Zimmermann R., Hayn M., Theussl C., Waeg G., Wagner E., Sattler W., Magin T.M., Wagner E.F., Zechner R. Hormone-sensitive lipase deficiency in mice causes diglyceride accumulation in adipose tissue, muscle, and testis. J. Biol. Chem. 2002;277:4806–4815. doi: 10.1074/jbc.M110355200. PubMed DOI

Fredrikson G., Strålfors P., Nilsson N.Ö., Belfrage P. Hormone-Sensitive Lipase from Adipose Tissue of Rat. Methods Enzymol. 1981;71:636–646. PubMed

Watt M.J., Carey A.L., Wolsk-Petersen E., Kraemer F.B., Pedersen B.K., Febbraio M.A. Hormone-sensitive lipase is reduced in the adipose tissue of patients with type 2 diabetes mellitus: Influence of IL-6 infusion. Diabetologia. 2005;48:105–112. doi: 10.1007/s00125-004-1598-x. PubMed DOI

Watt M.J., Heigenhauser G.J., Spriet L.L. Effects of dynamic exercise intensity on the activation of hormone-sensitive lipase in human skeletal muscle. J. Physiol. 2003;547:301–308. doi: 10.1113/jphysiol.2002.034595. PubMed DOI PMC

Holm C., Langin D., Manganiello V., Belfrage P., Degerman E. Regulation of hormone-sensitive lipase activity in adipose tissue. Lipases. 1997;286:45–67. PubMed

Richelsen B., Pedersen S.B., Kristensen K., Borglum J.D., Norrelund H., Christiansen J.S., Jorgensen J.O. Regulation of lipoprotein lipase and hormone-sensitive lipase activity and gene expression in adipose and muscle tissue by growth hormone treatment during weight loss in obese patients. Metabolism. 2000;49:906–911. doi: 10.1053/meta.2000.6738. PubMed DOI

Schweiger M., Schoiswohl G., Lass A., Radner F.P., Haemmerle G., Malli R., Graier W., Cornaciu I., Oberer M., Salvayre R., et al. The C-terminal region of human adipose triglyceride lipase affects enzyme activity and lipid droplet binding. J. Biol. Chem. 2008;283:17211–17220. doi: 10.1074/jbc.M710566200. PubMed DOI

Takagi A., Ikeda Y., Kobayashi K., Kobayashi K., Ikeda Y., Kozawa J., Miyauchi H., Li M., Hashimoto C., Hara Y., et al. Newly developed selective immunoinactivation assay revealed reduction in adipose triglyceride lipase activity in peripheral leucocytes from patients with idiopathic triglyceride deposit cardiomyovasculopathy. Biochem. Biophys. Res. Commun. 2018;495:646–651. doi: 10.1016/j.bbrc.2017.11.070. PubMed DOI

Chandak P.G., Radovic B., Aflaki E., Kolb D., Buchebner M., Frohlich E., Magnes C., Sinner F., Haemmerle G., Zechner R., et al. Efficient phagocytosis requires triacylglycerol hydrolysis by adipose triglyceride lipase. J. Biol. Chem. 2010;285:20192–20201. doi: 10.1074/jbc.M110.107854. PubMed DOI PMC

Reid B.N., Ables G.P., Otlivanchik O.A., Schoiswohl G., Zechner R., Blaner W.S., Goldberg I.J., Schwabe R.F., Chua S.C., Jr., Huang L.S. Hepatic overexpression of hormone-sensitive lipase and adipose triglyceride lipase promotes fatty acid oxidation, stimulates direct release of free fatty acids, and ameliorates steatosis. J. Biol. Chem. 2008;283:13087–13099. doi: 10.1074/jbc.M800533200. PubMed DOI PMC

Mersmann H.J. Lipoprotein and hormone-sensitive lipases in porcine adipose tissue. J. Anim. Sci. 1998;76:1396–1404. doi: 10.2527/1998.7651396x. PubMed DOI

Holm C., Olivecrona G., Ottosson M. Assays of lipolytic enzymes. Methods Mol. Biol. 2001;155:97–119. doi: 10.1385/1-59259-231-7:097. PubMed DOI

Sekiya M., Osuga J., Yahagi N., Okazaki H., Tamura Y., Igarashi M., Takase S., Harada K., Okazaki S., Iizuka Y., et al. Hormone-sensitive lipase is involved in hepatic cholesteryl ester hydrolysis. J. Lipid Res. 2008;49:1829–1838. doi: 10.1194/jlr.M800198-JLR200. PubMed DOI

Olzmann J.A., Carvalho P. Dynamics and functions of lipid droplets. Nat. Rev. Mol. Cell Biol. 2019;20:137–155. doi: 10.1038/s41580-018-0085-z. PubMed DOI PMC

Ding Y., Zhang S., Yang L., Na H., Zhang P., Zhang H., Wang Y., Chen Y., Yu J., Huo C., et al. Isolating lipid droplets from multiple species. Nat. Protoc. 2013;8:43–51. doi: 10.1038/nprot.2012.142. PubMed DOI

Brasaemle D.L., Wolins N.E. Isolation of Lipid Droplets from Cells by Density Gradient Centrifugation. Curr. Protoc. Cell Biol. 2016;72:3.15.1–3.15.13. doi: 10.1002/cpcb.10. PubMed DOI PMC

Borg M.L., Andrews Z.B., Duh E.J., Zechner R., Meikle P.J., Watt M.J. Pigment epithelium-derived factor regulates lipid metabolism via adipose triglyceride lipase. Diabetes. 2011;60:1458–1466. doi: 10.2337/db10-0845. PubMed DOI PMC

Bradley D.C., Kaslow H.R. Radiometric assays for glycerol, glucose, and glycogen. Anal. Biochem. 1989;180:11–16. doi: 10.1016/0003-2697(89)90081-X. PubMed DOI

Slavin B.G., Ong J.M., Kern P.A. Hormonal regulation of hormone-sensitive lipase activity and mRNA levels in isolated rat adipocytes. J. Lipid Res. 1994;35:1535–1541. doi: 10.1016/S0022-2275(20)41151-4. PubMed DOI

Amols H.I., Zaider M., Weinberger J., Ennis R., Schiff P.B., Reinstein L.E. Dosimetric considerations for catheter-based beta and gamma emitters in the therapy of neointimal hyperplasia in human coronary arteries. Int. J. Radiat. Oncol. Biol. Phys. 1996;36:913–921. doi: 10.1016/S0360-3016(96)00301-X. PubMed DOI

Morak M., Schmidinger H., Riesenhuber G., Rechberger G.N., Kollroser M., Haemmerle G., Zechner R., Kronenberg F., Hermetter A. Adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) deficiencies affect expression of lipolytic activities in mouse adipose tissues. Mol. Cell. Proteom. 2012;11:1777–1789. doi: 10.1074/mcp.M111.015743. PubMed DOI PMC

Witters L.A., Watts T.D., Daniels D.L., Evans J.L. Insulin stimulates the dephosphorylation and activation of acetyl-CoA carboxylase. Proc. Natl. Acad. Sci. USA. 1988;85:5473–5477. doi: 10.1073/pnas.85.15.5473. PubMed DOI PMC

Gregolin C., Ryder E., Kleinschmidt A.K., Warner R.C., Lane M.D. Molecular characteristics of liver acetyl CoA carboxylase. Proc. Natl. Acad. Sci. USA. 1966;56:148–155. doi: 10.1073/pnas.56.1.148. PubMed DOI PMC

Dean D., Daugaard J.R., Young M.E., Saha A., Vavvas D., Asp S., Kiens B., Kim K.H., Witters L., Richter E.A., et al. Exercise diminishes the activity of acetyl-CoA carboxylase in human muscle. Diabetes. 2000;49:1295–1300. doi: 10.2337/diabetes.49.8.1295. PubMed DOI

Moibi J.A., Ekpe E.D., Christopherson R.J. Acetyl-CoA carboxylase and fatty acid synthase activity and immunodetectable protein in adipose tissues of ruminants: Effect of temperature and feeding level. J. Anim. Sci. 2000;78:2383–2392. doi: 10.2527/2000.7892383x. PubMed DOI

Stansbie D., Brownsey R.W., Crettaz M., Denton R.M. Acute effects in vivo of anti-insulin serum on rates of fatty acid synthesis and activities of acetyl-coenzyme A carboxylase and pyruvate dehydrogenase in liver and epididymal adipose tissue of fed rats. Biochem. J. 1976;160:413–416. doi: 10.1042/bj1600413. PubMed DOI PMC

Halestrap A.P., Denton R.M. Hormonal regulation of adipose-tissue acetyl-Coenzyme A carboxylase by changes in the polymeric state of the enzyme. The role of long-chain fatty acyl-Coenzyme A thioesters and citrate. Biochem. J. 1974;142:365–377. doi: 10.1042/bj1420365. PubMed DOI PMC

Bijleveld C., Geelen M.J. Measurement of acetyl-CoA carboxylase activity in isolated hepatocytes. Biochim. Biophys. Acta. 1987;918:274–283. doi: 10.1016/0005-2760(87)90231-1. PubMed DOI

Witters L.A., Moriarity D., Martin D.B. Regulation of hepatic acetyl coenzyme A carboxylase by insulin and glucagon. J. Biol. Chem. 1979;254:6644–6649. doi: 10.1016/S0021-9258(18)50417-8. PubMed DOI

Thampy K.G., Wakil S.J. Activation of acetyl-CoA carboxylase. Purification and properties of a Mn2+-dependent phosphatase. J. Biol. Chem. 1985;260:6318–6323. doi: 10.1016/S0021-9258(18)88973-6. PubMed DOI

Wong K., Meyers R., Cantley L.C. Subcellular locations of phosphatidylinositol 4-kinase isoforms. J. Biol. Chem. 1997;272:13236–13241. doi: 10.1074/jbc.272.20.13236. PubMed DOI

Zimmermann R., Haemmerle G., Wagner E.M., Strauss J.G., Kratky D., Zechner R. Decreased fatty acid esterification compensates for the reduced lipolytic activity in hormone-sensitive lipase-deficient white adipose tissue. J. Lipid Res. 2003;44:2089–2099. doi: 10.1194/jlr.M300190-JLR200. PubMed DOI

Chung C.C., Ohwaki K., Schneeweis J.E., Stec E., Varnerin J.P., Goudreau P.N., Chang A., Cassaday J., Yang L., Yamakawa T., et al. A fluorescence-based thiol quantification assay for ultra-high-throughput screening for inhibitors of coenzyme A production. Assay Drug Dev. Technol. 2008;6:361–374. doi: 10.1089/adt.2007.105. PubMed DOI

Cerne D., Zitnik I.P., Sok M. Increased fatty acid synthase activity in non-small cell lung cancer tissue is a weaker predictor of shorter patient survival than increased lipoprotein lipase activity. Arch. Med. Res. 2010;41:405–409. doi: 10.1016/j.arcmed.2010.08.007. PubMed DOI

Topolska M., Martinez-Montanes F., Ejsing C.S. A Simple and Direct Assay for Monitoring Fatty Acid Synthase Activity and Product-Specificity by High-Resolution Mass Spectrometry. Biomolecules. 2020;10:118. doi: 10.3390/biom10010118. PubMed DOI PMC

Jayakumar A., Tai M.H., Huang W.Y., al-Feel W., Hsu M., Abu-Elheiga L., Chirala S.S., Wakil S.J. Human fatty acid synthase: Properties and molecular cloning. Proc. Natl. Acad. Sci. USA. 1995;92:8695–8699. doi: 10.1073/pnas.92.19.8695. PubMed DOI PMC

Dils R., Carey E.M. Fatty acid synthase from rabbit mammary gland. Methods Enzymol. 1975;35:74–83. doi: 10.1016/0076-6879(75)35140-9. PubMed DOI

Nepokroeff C.M., Lakshmanan M.R., Porter J.W. Fatty-acid synthase from rat liver. Methods Enzymol. 1975;35:37–44. doi: 10.1016/0076-6879(75)35136-7. PubMed DOI

Alwarawrah Y., Hughes P., Loiselle D., Carlson D.A., Darr D.B., Jordan J.L., Xiong J., Hunter L.M., Dubois L.G., Thompson J.W., et al. Fasnall, a Selective FASN Inhibitor, Shows Potent Anti-tumor Activity in the MMTV-Neu Model of HER2(+) Breast Cancer. Cell Chem. Biol. 2016;23:678–688. doi: 10.1016/j.chembiol.2016.04.011. PubMed DOI PMC

Najjar S.M., Yang Y., Fernstrom M.A., Lee S.J., Deangelis A.M., Rjaily G.A., Al-Share Q.Y., Dai T., Miller T.A., Ratnam S., et al. Insulin acutely decreases hepatic fatty acid synthase activity. Cell Metab. 2005;2:43–53. doi: 10.1016/j.cmet.2005.06.001. PubMed DOI

Roncari D.A. Fatty acid synthase from human liver. Methods Enzymol. 1981;71:73–79. doi: 10.1016/0076-6879(81)71011-5. PubMed DOI

Brusselmans K., Vrolix R., Verhoeven G., Swinnen J.V. Induction of cancer cell apoptosis by flavonoids is associated with their ability to inhibit fatty acid synthase activity. J. Biol. Chem. 2005;280:5636–5645. doi: 10.1074/jbc.M408177200. PubMed DOI

Hsu R.Y., Butterworth P.H.W., Porter J.W. Pigeon Liver Fatty Acid Synthase. Methods Enzymol. 1969;14:33–39.

Moustaid N., Hainque B., Quignard-Boulange A. Dexamethasone regulation of terminal differentiation in 3T3-F442A preadipocyte cell line. Cytotechnology. 1988;1:285–293. doi: 10.1007/BF00365073. PubMed DOI

Puig T., Turrado C., Benhamu B., Aguilar H., Relat J., Ortega-Gutierrez S., Casals G., Marrero P.F., Urruticoechea A., Haro D., et al. Novel Inhibitors of Fatty Acid Synthase with Anticancer Activity. Clin. Cancer Res. 2009;15:7608–7615. doi: 10.1158/1078-0432.CCR-09-0856. PubMed DOI

Lin H.P., Cheng Z.L., He R.Y., Song L., Tian M.X., Zhou L.S., Groh B.S., Liu W.R., Ji M.B., Ding C., et al. Destabilization of Fatty Acid Synthase by Acetylation Inhibits De Novo Lipogenesis and Tumor Cell Growth. Cancer Res. 2016;76:6924–6936. doi: 10.1158/0008-5472.CAN-16-1597. PubMed DOI PMC

Moustaid N., Jones B.H., Taylor J.W. Insulin increases lipogenic enzyme activity in human adipocytes in primary culture. J. Nutr. 1996;126:865–870. doi: 10.1093/jn/126.4.865. PubMed DOI

Wang Y., Jones Voy B., Urs S., Kim S., Soltani-Bejnood M., Quigley N., Heo Y.R., Standridge M., Andersen B., Dhar M., et al. The human fatty acid synthase gene and de novo lipogenesis are coordinately regulated in human adipose tissue. J. Nutr. 2004;134:1032–1038. doi: 10.1093/jn/134.5.1032. PubMed DOI

Xue B., Zemel M.B. Relationship between Human Adipose Tissue Agouti and Fatty Acid Synthase (FAS) J. Nutr. 2000;130:2478–2481. doi: 10.1093/jn/130.10.2478. PubMed DOI

Chiu S., Mulligan K., Schwarz J.M. Dietary carbohydrates and fatty liver disease: De novo lipogenesis. Curr. Opin. Clin. Nutr. Metab. Care. 2018;21:277–282. doi: 10.1097/MCO.0000000000000469. PubMed DOI

Jelenik T., Kaul K., Sequaris G., Flogel U., Phielix E., Kotzka J., Knebel B., Fahlbusch P., Horbelt T., Lehr S., et al. Mechanisms of Insulin Resistance in Primary and Secondary Nonalcoholic Fatty Liver. Diabetes. 2017;66:2241–2253. doi: 10.2337/db16-1147. PubMed DOI PMC

Eissing L., Scherer T., Todter K., Knippschild U., Greve J.W., Buurman W.A., Pinnschmidt H.O., Rensen S.S., Wolf A.M., Bartelt A., et al. De novo lipogenesis in human fat and liver is linked to ChREBP-beta and metabolic health. Nat. Commun. 2013;4:1528. doi: 10.1038/ncomms2537. PubMed DOI PMC

Simeone P., Tacconi S., Longo S., Lanuti P., Bravaccini S., Pirini F., Ravaioli S., Dini L., Giudetti A.M. Expanding Roles of De Novo Lipogenesis in Breast Cancer. Int. J. Environ. Res. Public Health. 2021;18:3575. doi: 10.3390/ijerph18073575. PubMed DOI PMC

Hellerstein M.K., Schwarz J.M., Neese R.A. Regulation of hepatic de novo lipogenesis in humans. Annu. Rev. Nutr. 1996;16:523–557. doi: 10.1146/annurev.nu.16.070196.002515. PubMed DOI

Rios-Esteves J., Resh M.D. Stearoyl CoA desaturase is required to produce active, lipid-modified Wnt proteins. Cell Rep. 2013;4:1072–1081. doi: 10.1016/j.celrep.2013.08.027. PubMed DOI PMC

Green C.D., Ozguden-Akkoc C.G., Wang Y., Jump D.B., Olson L.K. Role of fatty acid elongases in determination of de novo synthesized monounsaturated fatty acid species. J. Lipid Res. 2010;51:1871–1877. doi: 10.1194/jlr.M004747. PubMed DOI PMC

Lehner R., Kuksis A. Biosynthesis of triacylglycerols. Prog. Lipid Res. 1996;35:169–201. doi: 10.1016/0163-7827(96)00005-7. PubMed DOI

Izumi A., Hiraguchi H., Kodaka M., Ikeuchi E., Narita J., Kobayashi R., Matsumoto Y., Suzuki T., Yamamoto Y., Sato R., et al. MIG12 is involved in the LXR activation-mediated induction of the polymerization of mammalian acetyl-CoA carboxylase. Biochem. Biophys. Res. Commun. 2021;567:138–142. doi: 10.1016/j.bbrc.2021.06.040. PubMed DOI

Wei J., Tong L. How Does Polymerization Regulate Human Acetyl-CoA Carboxylase 1? Biochemistry. 2018;57:5495–5496. doi: 10.1021/acs.biochem.8b00881. PubMed DOI

Lawitz E.J., Coste A., Poordad F., Alkhouri N., Loo N., McColgan B.J., Tarrant J.M., Nguyen T., Han L., Chung C., et al. Acetyl-CoA Carboxylase Inhibitor GS-0976 for 12 Weeks Reduces Hepatic De Novo Lipogenesis and Steatosis in Patients With Nonalcoholic Steatohepatitis. Clin. Gastroenterol. Hepatol. 2018;16:1983–1991.e3. doi: 10.1016/j.cgh.2018.04.042. PubMed DOI

Wang C., Ma J., Zhang N., Yang Q., Jin Y., Wang Y. The acetyl-CoA carboxylase enzyme: A target for cancer therapy? Expert Rev. Anticancer Ther. 2015;15:667–676. doi: 10.1586/14737140.2015.1038246. PubMed DOI

Smith S., Witkowski A., Joshi A.K. Structural and functional organization of the animal fatty acid synthase. Prog. Lipid Res. 2003;42:289–317. doi: 10.1016/S0163-7827(02)00067-X. PubMed DOI

Jensen-Urstad A.P., Semenkovich C.F. Fatty acid synthase and liver triglyceride metabolism: Housekeeper or messenger? Biochim. Biophys. Acta. 2012;1821:747–753. doi: 10.1016/j.bbalip.2011.09.017. PubMed DOI PMC

Rysman E., Brusselmans K., Scheys K., Timmermans L., Derua R., Munck S., Van Veldhoven P.P., Waltregny D., Daniels V.W., Machiels J., et al. De novo lipogenesis protects cancer cells from free radicals and chemotherapeutics by promoting membrane lipid saturation. Cancer Res. 2010;70:8117–8126. doi: 10.1158/0008-5472.CAN-09-3871. PubMed DOI

Menendez J.A., Lupu R. Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nat. Rev. Cancer. 2007;7:763–777. doi: 10.1038/nrc2222. PubMed DOI

Zhou W., Han W.F., Landree L.E., Thupari J.N., Pinn M.L., Bililign T., Kim E.K., Vadlamudi A., Medghalchi S.M., El Meskini R., et al. Fatty acid synthase inhibition activates AMP-activated protein kinase in SKOV3 human ovarian cancer cells. Cancer Res. 2007;67:2964–2971. doi: 10.1158/0008-5472.CAN-06-3439. PubMed DOI