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Medium- and long-chain triglyceride propofol reduces the activity of acetyl-coenzyme A carboxylase in hepatic lipid metabolism in HepG2 and Huh7 cells

  • Wang, Li-yuan (Center for Anesthesiology, Beijing Anzhen Hospital, Capital Medical University) ;
  • Wu, Jing (North China University of Science and Technology) ;
  • Gao, Ya-fen (Center for Anesthesiology, Beijing Anzhen Hospital, Capital Medical University) ;
  • Lin, Duo-mao (Center for Anesthesiology, Beijing Anzhen Hospital, Capital Medical University) ;
  • Ma, Jun (Center for Anesthesiology, Beijing Anzhen Hospital, Capital Medical University)
  • 투고 : 2019.05.23
  • 심사 : 2019.09.02
  • 발행 : 2020.01.01

초록

Medium- and long-chain triglyceride (MCT/LCT) propofol is widely used as an intravenous anesthetic, especially in the intensive care unit. The present study aimed to assess whether MCT/LCT propofol is safe in the hyperlipidemic population for long-term use. Free fatty acids (FFAs) were used to establish high-fat stimulation of HepG2 and Huh7 cells. Subsequently, these cells were treated with propofol at the concentration of 0, 4, or 8 ㎍/ml for 24 and 48 h. The results indicated that the cell viability was notably decreased when the cells were stimulated with 2 mmol/L FFAs and treated with 12 ㎍/ml MCT/LCT propofol. Accordingly, we chose 2 mmol/L FFAs along with 4 and 8 ㎍/ml MCT/LCT propofol for the subsequent experiments. Four and 8 ㎍/ml MCT/LCT propofol inhibited FFA-induced lipid accumulation in the cells and significantly reversed acetyl coenzyme A carboxylase (ACC) activity. In addition, MCT/LCT propofol not only significantly promoted the phosphorylation of AMPK and ACC, but also reversed the FFA-induced decreased phosphorylation of AMPK and ACC. In conclusion, MCT/LCT propofol reverses the negative effects caused by FFAs in HepG2 and Huh7 cells, indicating that MCT/LCT propofol might positively regulate lipid metabolism.

키워드

참고문헌

  1. Erickson SK. Nonalcoholic fatty liver disease. J Lipid Res. 2009;50 Suppl:S412-S416. https://doi.org/10.1194/jlr.R800089-JLR200
  2. Day CP, James OF. Steatohepatitis: a tale of two "hits"? Gastroenterology. 1998;114:842-845. https://doi.org/10.1016/S0016-5085(98)70599-2
  3. Singla B, Malde AD. A prospective observational study of injection pain in children with medium plus long chain triglyceride and long chain triglyceride propofol premixed with lignocaine. Indian J Anaesth. 2018;62:214-218. https://doi.org/10.4103/ija.IJA_506_17
  4. Yew WS, Chong SY, Tan KH, Goh MH. The effects of intravenous lidocaine on pain during injection of medium- and long-chain triglyceride propofol emulsions. Anesth Analg. 2005;100:1693-1695. https://doi.org/10.1213/01.ANE.0000151718.58709.0B
  5. Theilen HJ, Adam S, Albrecht MD, Ragaller M. Propofol in a medium- and long-chain triglyceride emulsion: pharmacological characteristics and potential beneficial effects. Anesth Analg. 2002;95:923-929. https://doi.org/10.1213/00000539-200210000-00024
  6. Wu GJ, Lin YW, Tsai HC, Lee YW, Chen JT, Chen RM. Sepsisinduced liver dysfunction was ameliorated by propofol via suppressing hepatic lipid peroxidation, inflammation, and drug interactions. Life Sci . 2018;213:279-286. https://doi.org/10.1016/j.lfs.2018.10.038
  7. Tsuchiya H, Ueno T, Tanaka T, Matsuura N, Mizogami M. Comparative study on determination of antioxidant and membrane activities of propofol and its related compounds. Eur J Pharm Sci. 2010;39:97-102. https://doi.org/10.1016/j.ejps.2009.11.001
  8. Ge M, Yao W, Wang Y, Yuan D, Chi X, Luo G, Hei Z. Propofol alleviates liver oxidative stress via activating Nrf2 pathway. J Surg Res. 2015;196:373-381. https://doi.org/10.1016/j.jss.2015.03.016
  9. Kobayashi K, Yoshino F, Takahashi SS, Todoki K, Maehata Y, Komatsu T, Yoshida K, Lee MC. Direct assessments of the antioxidant effects of propofol medium chain triglyceride/long chain triglyceride on the brain of stroke-prone spontaneously hypertensive rats using electron spin resonance spectroscopy. Anesthesiology. 2008; 109:426-35. https://doi.org/10.1097/ALN.0b013e318182a903
  10. Musso G, Gambino R, Cassader M. Recent insights into hepatic lipid metabolism in non-alcoholic fatty liver disease (NAFLD). Prog Lipid Res. 2009;48:1-26. https://doi.org/10.1016/j.plipres.2008.08.001
  11. Hastings IM, Hill WG. Analysis of lines of mice selected for fat content. 2. correlated responses in the activities of enzymes involved in lipogenesis. Genet Res. 1990;55:55-61. https://doi.org/10.1017/S0016672300025192
  12. Savage DB, Choi CS, Samuel VT, Liu ZX, Zhang D, Wang A, Zhang XM, Cline GW, Yu XX, Geisler JG, Bhanot S, Monia BP, Shulman GI. Reversal of diet-induced hepatic steatosis and hepatic insulin resistance by antisense oligonucleotide inhibitors of acetyl-CoA carboxylases 1 and 2. J Clin Invest. 2006;116:817-824. https://doi.org/10.1172/JCI27300
  13. Abu-Elheiga L, Matzuk MM, Kordari P, Oh W, Shaikenov T, Gu Z, Wakil SJ. Mutant mice lacking acetyl-CoA carboxylase 1 are embryonically lethal. Proc Natl Acad Sci U S A. 2005;102:12011-12016. https://doi.org/10.1073/pnas.0505714102
  14. Woo M, Song YO, Kang KH, Noh JS. Anti-obesity effects of collagen peptide derived from skate (raja kenojei) skin through regulation of lipid metabolism. Mar Drugs. 2018;16:E306. https://doi.org/10.3390/md16090306
  15. Yang X, Xu P, Zhang F, Zhang L, Zheng Y, Hu M, Wang L, Han TL, Peng C, Wang L, Wen L, Zeng Y, Gao R, Xia Y, Tong C, Yang Z, Qi H, Baker PN. AMPK Hyper-Activation Alters Fatty Acids Metabolism and Impairs Invasiveness of Trophoblasts in Preeclampsia. Cell Physiol Biochem. 2018;49:578-594. https://doi.org/10.1159/000492995
  16. Ma J, Kang SY, Meng X, Kang AN, Park JH, Park YK, Jung HW. Effects of rhizome extract of dioscorea batatas and its active compound, allantoin, on the regulation of myoblast differentiation and mitochondrial biogenesis in c2c12 myotubes. Molecules. 2018;23:E2023. https://doi.org/10.3390/molecules23082023
  17. Huang Y, Hao J, Tian D, Wen Y, Zhao P, Chen H, Lv Y, Yang X. Antidiabetic Activity of a Flavonoid-Rich Extract From Sophora davidii (Franch.) Skeels in KK-Ay Mice via Activation of AMP-Activated Protein Kinase. Front Pharmacol. 2018;9:760. https://doi.org/10.3389/fphar.2018.00760
  18. Ruderman N, Prentki M. AMP kinase and malonyl-CoA: targets for therapy of the metabolic syndrome. Nat Rev Drug Discov. 2004; 3:340-351. https://doi.org/10.1038/nrd1344
  19. Dihingia A, Bordoloi J, Dutta P, Kalita J, Manna P. Hexane-isopropanolic extract of Tungrymbai, a North-East Indian fermented soybean food prevents hepatic steatosis via regulating AMPK-mediated SREBP/FAS/ACC/HMGCR and PPAR$\alpha$/CPT1A/UCP2 pathways. Sci Rep. 2018;8:10021. https://doi.org/10.1038/s41598-018-27607-7
  20. Jung S, Son H, Hwang CE, Cho KM, Park SW, Kim HJ. Ganoderma lucidum ameliorates non-alcoholic steatosis by upregulating energy metabolizing enzymes in the liver. J Clin Med. 2018;7:E152. https://doi.org/10.3390/jcm7060152
  21. Li RZ, Fan XX, Duan FG, Jiang ZB, Pan HD, Luo LX, Zhou YL, Li Y, Yao YJ, Yao XJ, Leung ELH, Liu L. Proscillaridin A induces apoptosis and suppresses non-small-cell lung cancer tumor growth via calcium-induced DR4 upregulation. Cell Death Dis. 2018;9:696. https://doi.org/10.1038/s41419-018-0733-4
  22. Hao J, Huang K, Chen C, Liang Y, Wang Y, Zhang X, Huang H. Polydatin improves glucose and lipid metabolisms in insulinresistant HepG2 cells through the AMPK pathway. Biol Pharm Bull. 2018;41:891-898. https://doi.org/10.1248/bpb.b17-01027
  23. Gong T, Ning X, Deng Z, Liu M, Zhou B, Chen X, Huang S, Xu Y, Chen Z, Luo R. Propofol-induced miR-219-5p inhibits growth and invasion of hepatocellular carcinoma through suppression of GPC3-mediated Wnt/${\beta}$-catenin signalling activation. J Cell Biochem. 2019;120:16934-16945. https://doi.org/10.1002/jcb.28952
  24. Zhang J, Shan WF, Jin TT, Wu GQ, Xiong XX, Jin HY, Zhu SM. Propofol exerts anti-hepatocellular carcinoma by microvesiclemediated transfer of miR-142-3p from macrophage to cancer cells. J Transl Med. 2014;12:279. https://doi.org/10.1186/s12967-014-0279-x
  25. Shirwany NA, Zou MH. AMPK: a cellular metabolic and redox sensor. A minireview. Front Biosci (Landmark Ed). 2014;19:447-474. https://doi.org/10.2741/4218
  26. Carling D, Hardie DG. The substrate and sequence specificity of the AMP-activated protein kinase. Phosphorylation of glycogen synthase and phosphorylase kinase. Biochim Biophys Acta. 1989;1012:81-86. https://doi.org/10.1016/0167-4889(89)90014-1
  27. Kahn BB, Alquier T, Carling D, Hardie DG. AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab. 2005;1:15-25. https://doi.org/10.1016/j.cmet.2004.12.003
  28. Bijland S, Mancini SJ, Salt IP. Role of AMP-activated protein kinase in adipose tissue metabolism and inflammation. Clin Sci (Lond). 2013;124:491-507. https://doi.org/10.1042/CS20120536
  29. Hardie DG. AMP-activated protein kinase: maintaining energy homeostasis at the cellular and whole-body levels. Annu Rev Nutr. 2014;34:31-55. https://doi.org/10.1146/annurev-nutr-071812-161148
  30. Lin SC, Hardie DG. AMPK: Sensing Glucose as well as Cellular Energy Status. Cell Metab. 2018;27:299-313. https://doi.org/10.1016/j.cmet.2017.10.009
  31. Day EA, Ford RJ, Steinberg GR. AMPK as a Therapeutic Target for Treating Metabolic Diseases. Trends Endocrinol Metab. 2017; 28:545-560. https://doi.org/10.1016/j.tem.2017.05.004
  32. Liu H, Liu M, Jin Z, Yaqoob S, Zheng M, Cai D, Liu J, Guo S. Ginsenoside Rg2 inhibits adipogenesis in 3T3-L1 preadipocytes and suppresses obesity in high-fat-diet-induced obese mice through the AMPK pathway. Food Funct. 2019;10:3603-3614. https://doi.org/10.1039/C9FO00027E
  33. Tsuji H, Kasai M, Takeuchi H, Nakamura M, Okazaki M, Kondo K. Dietary medium-chain triacylglycerols suppress accumulation of body fat in a double-blind, controlled trial in healthy men and women. J Nutr. 2001;131:2853-2859. https://doi.org/10.1093/jn/131.11.2853