The Role of Stearoyl-coenzyme A Desaturase 1 in Liver Development, Function, and Pathogenesis
Main Article Content
Keywords
hepatic lipogenesis, hydroxy pyridine, MK-8245, stearoyl-coenzyme A desaturase 1, SCD1
Abstract
Stearoyl-coenzyme A desaturase 1 (SCD1) is a microsomal enzyme that controls fatty acid metabolism and is highly expressed in hepatocytes. SCD1 may play a key role in liver development and hepatic lipid homeostasis through promoting monounsaturated protein acylation and converting lipotoxic saturated fatty acids into monounsaturated fatty acids. Imbalanced activity of SCD1 has been implicated in fatty liver induction, inflammation and stress. In this review, the role of SCD1 in hepatic development, function and pathogenesis is discussed. Additionally, emerging novel therapeutic agents targeting SCD1 for the treatment of liver disorders are presented.
References
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2. Flowers MT, Ntambi JM. Role of stearoyl-coenzyme A desaturase in regulating lipid metabolism. Curr Opin Lipidol. 2008 Jun;19(3):248–56. https://doi.org/10.1097/MOL.0b013e3282f9b54d
3. Arregui M, Buijsse B, Stefan N, Corella D, Fisher E, di Giuseppe R, et al. Heterogeneity of the Stearoyl-CoA desaturase-1 (SCD1) gene and metabolic risk factors in the EPIC-Potsdam study. PLoS One. 2012;7:e48338. https://doi.org/10.1371/journal.pone.0048338
4. Mauvoisin D, Charfi C, Lounis AM, Rassart E, Mounier C. Decreasing stearoyl-CoA desaturase-1 expression inhibits ?-catenin signaling in breast cancer cells. Cancer Sci. 2013 Jan;104(1):36–42. Available from: https://doi.org/10.1111/cas.12032
5. Zhang L, Ge L, Tran T, Stenn K, Prouty SM. Isolation and characterization of the human stearoyl-CoA desaturase gene promoter: Requirement of a conserved CCAAT cis-element. Biochem J. 2001;357:183–93. https://doi.org/10.1042/bj3570183
6. Bai Y, McCoy JG, Levin EJ, Sobrado P, Rajashankar KR, Fox BG, et al. X-ray structure of a mammalian stearoyl-CoA desaturase. Nature. 2015 Aug;524(7564):252–6. Available from: https://doi.org/10.1038/nature14549
7. Mehdizadeh A, Fayezi S, Darabi M. SCD (stearoyl-CoA desaturase (delta-9-desaturase)). Atlas Genet Cytogenet Oncol Haematol. 2016;20(2):77–80. https://doi.org/10.4267/2042/62515
8. Kim YC, Gomez FE, Fox BG, Ntambi JM. Differential regulation of the stearoyl-CoA desaturase genes by thiazolidinediones in 3T3-L1 adipocytes. J Lipid Res [Internet]. 2000 Aug;41(8):1310–16. Available from (accessed 25.12.18.): http://www.ncbi.nlm.nih.gov/pubmed/10946019
9. Miyazaki M, Dobrzyn A, Man WC, Chu K, Sampath H, Kim H-J, et al. Stearoyl-CoA Desaturase 1 gene expression is necessary for fructose-mediated induction of lipogenic gene expression by sterol regulatory element-binding protein-1c-dependent and -independent mechanisms. J Biol Chem. 2004 Jun;279(24):25164–71. https://doi.org/10.1074/jbc.M402781200
10. Steinhart Z, Angers S. Wnt signaling in development and tissue homeostasis. Development. 2018;145(11):1–8. https://doi.org/10.1242/dev.146589
11. Janda CY, Waghray D, Levin AM, Thomas C, Garcia KC. Structural basis of Wnt recognition by Frizzled. Science. 2012 Jul;337(6090):59–64. https://doi.org/10.1126/science.1222879
12. Sekine K, Takebe T, Taniguchi H. Liver regeneration using cultured liver bud. Methods Mol Biol. 2017;1597:207–16. https://doi.org/10.1007/978-1-4939-6949-4_15
13. Gualdi R, Bossard P, Zheng M, Hamada Y, Coleman JR, Zaret KS. Hepatic specification of the gut endoderm in vitro: Cell signaling and transcriptional control. Genes Dev. 1996 Jul;10(13):1670–82. https://doi.org/10.1101/gad.10.13.1670
14. Lokmane L, Haumaitre C, Garcia-Villalba P, Anselme I, Schneider-Maunoury S, Cereghini S. Crucial role of vHNF1 in vertebrate hepatic specification. Development. 2008 Aug;135(16):2777–86. https://doi.org/10.1242/dev.023010
15. Lemaigre FP. Mechanisms of liver development: Concepts for understanding liver disorders and design of novel therapies. Gastroenterology. 2009 Jul;137(1):62–79. https://doi.org/10.1053/j.gastro.2009.03.035
16. Rahimi Y, Mehdizadeh A, Nozad Charoudeh H, Nouri M, Valaei K, Fayezi S, et al. Hepatocyte differentiation of human induced pluripotent stem cells is modulated by stearoyl-CoA desaturase 1 activity. Dev Growth Differ. 2015 Dec;57(9):667–74. Available from: https://doi.org/10.1111/dgd.12255
17. Schröder E, Höhme S, Böttger J, Aleithe S, Gebhardt R, Matz-Soja M. Zonation of Morphogens in the adult liver – Crosstalk between Hh and Wnt/?-Catenin signaling. Z Gastroenterol. 2018 Jan;56(01):E2–89. https://doi.org/10.1055/s-0037-1612748
18. Brosch M, Kattler K, Herrmann A, von Schönfels W, Nordström K, Seehofer D, et al. Epigenomic map of human liver reveals principles of zonated morphogenic and metabolic control. Nat Commun. 2018 Oct;9(1):4150. https://doi.org/10.1038/s41467-018-06611-5
19. Preziosi M, Okabe H, Poddar M, Singh S, Monga SP. Endothelial Wnts regulate ?-catenin signaling in murine liver zonation and regeneration: A sequel to the Wnt-Wnt situation. Hepatol Commun. 2018 Jul;2(7):845–60. https://doi.org/10.1002/hep4.1196
20. Nelsen CJ, Rickheim DG, Timchenko NA, Stanley MW, Albrecht JH. Transient expression of cyclin D1 is sufficient to promote hepatocyte replication and liver growth in vivo. Cancer Res. 2001 Dec;61(23):8564–8.
21. Yu X, Wang Y, DeGraff DJ, Wills ML, Matusik RJ. Wnt/?-catenin activation promotes prostate tumor progression in a mouse model. Oncogene. 2011 Apr;30(16):1868–79. https://doi.org/10.1038/onc.2010.560
22. Dadhania VP, Bhushan B, Apte U, Mehendale HM. Wnt/?-Catenin signaling drives thioacetamide-mediated heteroprotection against acetaminophen-induced lethal liver injury. Dose Response. 15(1):1559325817690287. https://doi.org/10.1177/1559325817690287
23. Xu C, Lin F, Qin S. Relevance between lipid metabolism-associated genes and rat liver regeneration. Hepatol Res. 2008 Aug;38(8):825–37. https://doi.org/10.1111/j.1872-034X.2008.00345.x
24. Forbes SJ, Newsome PN. Liver regeneration—mechanisms and models to clinical application. Nat Rev Gastroenterol Hepatol. 2016;13(8):473–85. https://doi.org/10.1038/nrgastro.2016.97
25. Bellet MM, Masri S, Astarita G, Sassone-Corsi P, Della Fazia MA, Servillo G. Histone deacetylase SIRT1 controls proliferation, circadian rhythm, and lipid metabolism during liver regeneration in mice. J Biol Chem. 2016;291(44):23318–29. https://doi.org/10.1074/jbc.M116.737114
26. Kohjima M, Tsai T-H, Tackett BC, Thevananther S, Li L, Chang BH-J, et al. Delayed liver regeneration after partial hepatectomy in adipose differentiation related protein-null mice. J Hepatol. 2013 Dec;59(6):1246–54. https://doi.org/10.1016/j.jhep.2013.07.025
27. Collins JM, Neville MJ, Hoppa MB, Frayn KN. De novo lipogenesis and stearoyl-CoA desaturase are coordinately regulated in the human adipocyte and protect against palmitate-induced cell injury. J Biol Chem. 2010;285:6044–52. https://doi.org/10.1074/jbc.M109.053280
28. Singh V, Chassaing B, Zhang L, San Yeoh B, Xiao X, Kumar M, et al. Microbiota-dependent hepatic lipogenesis mediated by Stearoyl CoA Desaturase 1 (SCD1) promotes metabolic syndrome in TLR5-deficient mice. Cell Metab. 2015 Dec;22(6):983–96. https://doi.org/10.1016/j.cmet.2015.09.028
29. Miyazaki M, Sampath H, Liu X, Flowers MT, Chu K, Dobrzyn A, et al. Stearoyl-CoA desaturase-1 deficiency attenuates obesity and insulin resistance in leptin-resistant obese mice. Biochem Biophys Res Commun. 2009 Mar;380(4):818–22. https://doi.org/10.1016/j.bbrc.2009.01.183
30. Miyazaki M, Flowers MT, Sampath H, Chu K, Otzelberger C, Liu X, et al. Hepatic stearoyl-CoA desaturase-1 deficiency protects mice from carbohydrate-induced adiposity and hepatic steatosis. Cell Metab. 2007 Dec;6(6):484–96. https://doi.org/10.1016/j.cmet.2007.10.014
31. Sampath H, Miyazaki M, Dobrzyn A, Ntambi JM. Stearoyl-CoA desaturase-1 mediates the pro-lipogenic effects of dietary saturated fat. J Biol Chem. 2007 Jan;282(4):2483–93. Available from: https://doi.org/10.1074/jbc.M610158200
32. Liu G, Zhou L, Zhang H, Chen R, Zhang Y, Li L, et al. Regulation of hepatic lipogenesis by the zinc finger protein Zbtb20. Nat Commun. 2017 Mar;8:14824. https://doi.org/10.1038/ncomms14824
33. Gariani K, Ryu D, Menzies KJ, Yi H-S, Stein S, Zhang H, et al. Inhibiting poly ADP-ribosylation increases fatty acid oxidation and protects against fatty liver disease. J Hepatol. 2017;66(1):132–41. https://doi.org/10.1016/j.jhep.2016.08.024
34. Lounis MA, Escoula Q, Veillette C, Bergeron K-F, Ntambi JM, Mounier C. SCD1 deficiency protects mice against ethanol-induced liver injury. Biochim Biophys Acta. 2016;1861(11):1662–70. https://doi.org/10.1016/j.bbalip.2016.07.012
35. Amor AJ, Cofán M, Mateo-Gallego R, Cenarro A, Civeira F, Ortega E, et al. Dietary polyunsaturated fatty acids mediate the inverse association of stearoyl-CoA desaturase activity with the risk of fatty liver in dyslipidaemic individuals. Eur J Nutr. 2018 Apr; Available from: https://doi.org/10.1007/s00394-018-1691-4
36. Bond LM, Ntambi JM. UCP1 deficiency increases adipose tissue monounsaturated fatty acid synthesis and trafficking to the liver. J Lipid Res. 2018 Feb;59(2):224–36. Available from: https://doi.org/10.1194/jlr.M078469
37. Wek RC, Anthony TG. Obesity: Stressing about unfolded proteins. Nat Med. 2010 Apr;16(4):374–6.https://doi.org/10.1038/nm0410-374
38. Ron D, Walter P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol. 2007 Jul;8(7):519–29. https://doi.org/10.1038/nrm2199
39. Rocha DM, Caldas AP, Oliveira LL, Bressan J, Hermsdorff HH. Saturated fatty acids trigger TLR4-mediated inflammatory response. Atherosclerosis. 2016 Jan;244:211–5. https://doi.org/10.1016/j.atherosclerosis.2015.11.015
40. Lu H, Lei X, Zhang Q. Moderate activation of IKK2-NF-kB in unstressed adult mouse liver induces cytoprotective genes and lipogenesis without apparent signs of inflammation or fibrosis. BMC Gastroenterol. 2015 Jul;15:94. https://doi.org/10.1186/s12876-015-0325-z
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Feb 6, 2019
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The Role of Stearoyl-coenzyme A Desaturase 1 in Liver Development, Function, and Pathogenesis. (2019). Journal of Renal and Hepatic Disorders, 3(1), 15-22. https://doi.org/10.15586/jrenhep.2019.49
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Review Hepatology
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