Epigallocatechin-3-gallate ameliorates hepatic damages by relieve FGF21 resistance and promotion of FGF21–AMPK pathway in mice fed a high fat diet
Tóm tắt
Non-alcoholic fatty liver disease (NAFLD) is considered to be one of the most common chronic liver diseases across worldwide. Epigallocatechin-3-gallate (EGCG) derived from extract of green tea and is well known for beneficial effects on anti-oxidative, anti-inflammatory, and anti-tumor activity. The present study aimed to implore its underlying mechanism for protective effect of NAFLD. Mice were fed either high fat diet (HFD) or chow diet with or without EGCG treatment in HFD group, for up to 16 weeks. Histopathology, expression of lipid and glucose metabolism and lipogenesis-related gene expression were assessed. Primary mouse hepatocytes were treated with free fatty acids combined with different doses of EGCG for 48 h, expression of lipid and lipogenesis-related gene expression were assessed. The results showed that EGCG attenuated HFD- and FFA-induced lipid accumulation in vivo and in vitro. EGCG can decrease the oxidative stress and promote Nrf2 level. Meanwhile EGCG alleviated FGF21 resistance and elevated FGFR/AMPK expression, which suggested an unrecognized mechanism of EGCG in ameliorating NAFLD. EGCG attenuated hepatocytes damage and dysfunction in NAFLD by alleviating FGF21 resistance and improve FGFR/AMPK pathway, mitigating oxidative stress. Our studies verified that EGCG may become a promising drug to treat or relieve NAFLD.
Tài liệu tham khảo
Ahmed MH, Noor SK, Bushara SO, Husain NE, Elmadhoun WM, Ginawi IA, Osman MM, Mahmoud AO, Almobarak AO. Non-alcoholic fatty liver disease in africa and middle east: an attempt to predict the present and future implications on the healthcare system. Gastroenterol Res. 2017;10:271–9.
Li S, Hong M, Tan HY, Wang N, Feng Y. Insights into the role and interdependence of oxidative stress and inflammation in liver diseases. Oxid Med Cell Longev. 2016;2016:4234061.
Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, Harrison SA, Brunt EM, Sanyal AJ. The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the study of liver diseases. Hepatology. 2018;67:328–57.
Fazel Y, Koenig AB, Sayiner M, Goodman ZD, Younossi ZM. Epidemiology and natural history of non-alcoholic fatty liver disease. Metabolism. 2016;65:1017–25.
Reygaert WC. The antimicrobial possibilities of green tea. Front Microbiol. 2014;5:434.
Recio MC, Andujar I, Rios JL. Anti-inflammatory agents from plants: progress and potential. Curr Med Chem. 2012;19:2088–103.
Wu D, Liu Z, Wang Y, Zhang Q, Li J, Zhong P, Xie Z, Ji A, Li Y. Epigallocatechin-3-gallate alleviates high-fat diet-induced nonalcoholic fatty liver disease via inhibition of apoptosis and promotion of autophagy through the ROS/MAPK signaling pathway. Oxid Med Cell Longev. 2021;2021:5599997.
Bae UJ, Park J, Park IW, Chae BM, Oh MR, Jung SJ, Ryu GS, Chae SW, Park BH. Epigallocatechin-3-gallate-rich green tea extract ameliorates fatty liver and weight gain in mice fed a high fat diet by activating the sirtuin 1 and AMP activating protein kinase pathway. Am J Chin Med. 2018;46:617–32.
Katsiki N, Mantzoros C. Fibroblast growth factor 21: a role in cardiometabolic disorders and cardiovascular risk prediction? Metabolism. 2019;93:iii–v.
Liu J, Xu Y, Hu Y, Wang G. The role of fibroblast growth factor 21 in the pathogenesis of non-alcoholic fatty liver disease and implications for therapy. Metabolism. 2015;64:380–90.
He L, Deng L, Zhang Q, Guo J, Zhou J, Song W, Yuan F. Diagnostic value of CK-18, FGF-21, and related biomarker panel in nonalcoholic fatty liver disease: a systematic review and meta-analysis. Biomed Res Int. 2017;2017:9729107.
Badman MK, Pissios P, Kennedy AR, Koukos G, Flier JS, Maratos-Flier E. Hepatic fibroblast growth factor 21 is regulated by PPARalpha and is a key mediator of hepatic lipid metabolism in ketotic states. Cell Metab. 2007;5:426–37.
Lundåsen T, Hunt MC, Nilsson LM, Sanyal S, Angelin B, Alexson SE, Rudling M. PPARalpha is a key regulator of hepatic FGF21. Biochem Biophys Res Commun. 2007;360:437–40.
Chen Z, Tian R, She Z, Cai J, Li H. Role of oxidative stress in the pathogenesis of nonalcoholic fatty liver disease. Free Radical Biol Med. 2020;152:116–41.
Chau MD, Gao J, Yang Q, Wu Z, Gromada J. Fibroblast growth factor 21 regulates energy metabolism by activating the AMPK–SIRT1–PGC-1α pathway. Proc Natl Acad Sci USA. 2010;107:12553–8.
Jiang X, Chen J, Zhang C, Zhang Z, Tan Y, Feng W, Skibba M, Xin Y, Cai L. The protective effect of FGF21 on diabetesinduced male germ cell apoptosis is associated with up-regulated testicular AKT and AMPK/Sirt1/PGC-1α signaling. Endocrinology. 2015;156:1156–70.
Zhang N, Liu C, Zhang Y, Xu D, Gui L, Lu Y, Zhang Q. Liraglutide regulates lipid metabolism via FGF21–LKB1–AMPK–ACC1 pathway in white adipose tissues and macrophage of type 2 diabetic mice. Biochem Biophys Res Commun. 2021;548:120–6.
Chau MD, Gao J, Yang Q, Wu Z, Gromada J. Fibroblast growth factor 21 regulates energy metabolism by activating the AMPK–SIRT1–PGC-1alpha pathway. Proc Natl Acad Sci USA. 2010;107:12553–8.
Cyphert HA, Alonge KM, Ippagunta SM, Hillgartner FB. Glucagon stimulates hepatic FGF21 secretion through a PKA- and EPAC-dependent posttranscriptional mechanism. PloS ONE. 2014;9:e94996.
Sonoda J, Chen MZ, Baruch A. FGF21-receptor agonists: an emerging therapeutic class for obesity-related diseases. Horm Mol Biol Clin Investig. 2017. https://doi.org/10.1515/hmbci-2017-0002.
Dai S, Zhou Z, Chen Z, Xu G, Chen Y. Fibroblast growth factor receptors (FGFRs): structures and small molecule inhibitors. Cells. 2019;8:614.
Dushay J, Chui PC, Gopalakrishnan GS, Varela-Rey M, Crawley M, Fisher FM, Badman MK, Martinez-Chantar ML, Maratos-Flier E. Increased fibroblast growth factor 21 in obesity and nonalcoholic fatty liver disease. Gastroenterology. 2010;139:456–63.
Fisher FM, Chui PC, Antonellis PJ, Bina HA, Kharitonenkov A, Flier JS, Maratos-Flier E. Obesity is a fibroblast growth factor 21 (FGF21)-resistant state. Diabetes. 2010;59:2781–9.
Chakravarthy MV, Pan Z, Zhu Y, Tordjman K, Schneider JG, Coleman T, Turk J, Semenkovich CF. “New” hepatic fat activates PPARalpha to maintain glucose, lipid, and cholesterol homeostasis. Cell Metab. 2005;1:309–22.
Tucker B, Li H, Long X, Rye KA, Ong KL. Fibroblast growth factor 21 in non-alcoholic fatty liver disease. Metabolism. 2019;101:153994.
Santamarina AB, Oliveira JL, Silva FP, Carnier J, Mennitti LV, Santana AA, de Souza GH, Ribeiro EB, do OllerNascimento CM, Lira FS, Oyama LM. Green tea extract rich in epigallocatechin-3-gallate prevents fatty liver by AMPK activation via LKB1 in mice fed a high-fat diet. PloS ONE. 2015;10:e0141227.
Tan Y, Kim J, Cheng J, Ong M, Lao WG, Jin XL, Lin YG, Xiao L, Zhu XQ, Qu XQ. Green tea polyphenols ameliorate non-alcoholic fatty liver disease through upregulating AMPK activation in high fat fed Zucker fatty rats. World J Gastroenterol. 2017;23:3805–14.
Ferré P, Foufelle F. Hepatic steatosis: a role for de novo lipogenesis and the transcription factor SREBP-1c. Diabetes Obes Metab. 2010;12(Suppl 2):83–92.
Liu HW, Chan YC, Wang MF, Wei CC, Chang SJ. Dietary (−)-epigallocatechin-3-gallate supplementation counteracts aging-associated skeletal muscle insulin resistance and fatty liver in senescence-accelerated mouse. J Agric Food Chem. 2015;63:8407–17.
Henriksen BS, Curtis ME, Fillmore N, Cardon BR, Thomson DM, Hancock CR. The effects of chronic AMPK activation on hepatic triglyceride accumulation and glycerol 3-phosphate acyltransferase activity with high fat feeding. Diabetol Metab Syndr. 2013;5:29.
Kohjima M, Higuchi N, Kato M, Kotoh K, Yoshimoto T, Fujino T, Yada M, Yada R, Harada N, Enjoji M, Takayanagi R, Nakamuta M. SREBP-1c, regulated by the insulin and AMPK signaling pathways, plays a role in nonalcoholic fatty liver disease. Int J Mol Med. 2008;21:507–11.
Chen C, Liu Q, Liu L, Hu YY, Feng Q. Potential biological effects of (−)-epigallocatechin-3-gallate on the treatment of nonalcoholic fatty liver disease. Mol Nutr Food Res. 2018;62:1700483.