胆汁酸受体FXR对非酒精性脂肪性肝病糖脂代谢的作用研究进展*

doi:10.3969/j.issn.1672-5069.2025.04.003

Abstract

Shi Dandan, Ai Bichen, Ma Qixin, et al. Foles of bile acid FXR receptor on glycolipid metabolism in non-alcoholic fatty liver disease[J]. Journal of Practical Hepatology, 2025, 28(4): 489-492.

[1] Guo X, Yin X, Liu Z, et al. Non-alcoholic fatty liver disease (nafld) pathogenesis and natural products for prevention and treatment. Int J Mol Sci,2022,23(24):15489.
[2] Xu R, Pan J, Zhou W, et al. Recent advances in lean nafld. Biomed Pharmacother,2022,153:113331.
[3] Sakurai Y, Kubota N, Yamauchi T, et al. Role of insulin resistance in mafld. Int J Mol Sci,2021,22(8):4156.
[4] 杜沅沁,徐健,黄晶晶,等. 胆汁酸与糖脂代谢的关系及其在非酒精性脂肪性肝病中的发病机制及潜在价值. 生命化学,2022,42(10):1820-1827.
[5] Shibo C, Sili W, Yanfang Q, et al. Emerging trends and hotspots in the links between the bile acids and nafld from 2002 to 2022: a bibliometric analysis. Endocrinol Diabetes Metab,2024,7(1):e460.
[6] Wang J, Yang N, Xu Y. Natural products in the modulation of farnesoid x receptor against nonalcoholic fatty liver disease. Am J Chin Med,2024,52(2):291-314.
[7] Yang Z, Danzeng A, Liu Q, et al. The role of nuclear receptors in the pathogenesis and treatment of non-alcoholic fatty liver disease. Int J Biol Sci,2024,20(1):113-126.
[8] 赵瀚东,杨帆,詹丽. 非酒精性脂肪性肝病发病机制研究进展. 解放军医学院学报,2022,43(3):366-371.
[9] Forman B M, Goode E, Chen J, et al. Identification of a nuclear receptor that is activated by farnesol metabolites. Cell,1995,81(5):687-693.
[10] Makishima M, Okamoto A Y, Repa J J, et al. Identification of a nuclear receptor for bile acids. Science,1999, 284(5418):1362-1365.
[11] Adorini L, Trauner M. Fxr agonists in nash treatment. J Hepatol,2023,79(5):1317-1331.
[12] Guo Y, Xie G, Zhang X. Role of fxr in renal physiology and kidney diseases. Int J Mol Sci,2023,24(3):2408.
[13] Deng W, Fan W, Tang T, et al. Farnesoid x receptor deficiency induces hepatic lipid and glucose metabolism disorder via regulation of pyruvate dehydrogenase kinase 4. Oxid Med Cell Longev,2022,2022:3589525.
[14] Di Pasqua L G, Cagna M, Palladini g, et al.Fxr agonists int-787 and oca increase reck and inhibit liver steatosis and inflammation in diet-induced ob/ob mouse model of nash. Liver Int,2024,44(1):214-227.
[15] Moon AN, Briand F, Breyner N, et al. Improvement of nash and liver fibrosis through modulation of the gut-liver axis by a novel intestinal fxr agonist. Biomed Pharmacother,2024,173:116331.
[16] Shiragannavar V D, Sannappa Gowda N G, Puttahanumantharayappa L D, et al. The ameliorating effect of withaferin a on high-fat diet-induced non-alcoholic fatty liver disease by acting as an lxr/fxr dual receptor activator. Front Pharmacol,2023,14:1135952.
[17] Peng A, Liu S, Fang L, et al. Inonotus obliquus and its bioactive compounds alleviate non-alcoholic fatty liver disease via regulating fxr/shp/srebp-1c axis. Eur J Pharmacol,2022,921:174841.
[18] Jiang T, Wang X X, Scherzer P, et al. Farnesoid x receptor modulates renal lipid metabolism, fibrosis, and diabetic nephropathy. Diabetes,2007,56(10):2485-2493.
[19] Chen S, Sun S, Feng Y, et al. Diosgenin attenuates nonalcoholic hepatic steatosis through the hepatic fxr-shp-srebp1c/pparα/cd36 pathway. Eur J Pharmacol,2023,952:175808.
[20] Sagar N M, McFarlane M, Nwokolo C, et al. Mechanisms of triglyceride metabolism in patients with bile acid diarrhea. World J Gastroenterol,2016,22(30):6757-6763.
[21] D'Agati V D, Chagnac A, De Vries A P J, et al. Obesity-related glomerulopathy: clinical and pathologic characteristics and pathogenesis. Nat Rev Nephrol,2016,12(8):453-471.
[22] Röhrl C, Eigner K, Fruhwürth S, et al. Bile acids reduce endocytosis of high-density lipoprotein (hdl) in hepg2 cells. Plos One,2014,9(7):e102026.
[23] Ghosh Laskar M, Eriksson M, Rudling M, et al. Treatment with the natural fxr agonist chenodeoxycholic acid reduces clearance of plasma ldl whilst decreasing circulating pcsk9, lipoprotein(a) and apolipoprotein c-iii. J Intern Med,2017,281(6):575-585.
[24] Xu J, Li Y, Chen W-D, et al. Hepatic carboxylesterase 1 is essential for both normal and farnesoid x receptor-controlled lipid homeostasis. Hepatology,2014,59(5):1761-1771.
[25] Sun L, Cai J, Gonzalez F J. The role of farnesoid x receptor in metabolic diseases, and gastrointestinal and liver cancer. Nat Rev Gastroenterol Hepatol,2021,18(5):335-347.
[26] Panzitt K, Wagner M. Fxr in liver physiology: multiple faces to regulate liver metabolism. Biochim Biophys Acta Mol Basis Dis,2021,1867(7):166133.
[27] Zhang Y, Yin L, Anderson J, et al. Identification of novel pathways that control farnesoid x receptor-mediated hypocholesterolemia. J Biol Chem,2010,285(5):3035-3043.
[28] Chennamsetty I, Claudel T, Kostner K M, et al. Farnesoid x receptor represses hepatic human apoa gene expression. J Clin Invest,2011,121(9):3724-3734.
[29] Gautier T, De Haan W, Grober J, et al. Farnesoid x receptor activation increases cholesteryl ester transfer protein expression in humans and transgenic mice. J Lipid Res,2013,54(8):2195-2205.
[30] Dong B, Young M, Liu X, et al. Regulation of lipid metabolism by obeticholic acid in hyperlipidemic hamsters. J Lipid Res,2017,58(2):350-363.
[31] Fang S, Suh J M, Reilly S M, et al. Intestinal fxr agonism promotes adipose tissue browning and reduces obesity and insulin resistance. Nat Med,2015,21(2):159-165.
[32] Mudaliar S, Henry R R, Sanyal A J, et al. Efficacy and safety of the farnesoid x receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease. Gastroenterology,2013,145(3):574-582.
[33] Yamagata K, Daitoku H, Shimamoto Y, et al. Bile acids regulate gluconeogenic gene expression via small heterodimer partner-mediated repression of hepatocyte nuclear factor 4 and foxo1. J Biol Chem,2004,279(22):23158-23165.
[34] Potthoff M J, Boney-Montoya J, Choi M, et al. Fgf15/19 regulates hepatic glucose metabolism by inhibiting the creb-pgc-1α pathway. Cell Metab,2011,13(6):729-738.
[35] Caron S, Huaman Samanez C, Dehondt H, et al. Farnesoid x receptor inhibits the transcriptional activity of carbohydrate response element binding protein in human hepatocytes. Mol Cell Biol,2013,33(11):2202-2211.
[36] 李嘉鑫,于嘉祥,吕雪辉,等. 基于“土壅木郁”理论探讨益糖康调控FXR对T2DM大鼠肝糖原合成的影响. 中华中医药杂志,2023,38(5):2424-2429.
[37] Degirolamo C, Sabbà C, Moschetta A. Therapeutic potential of the endocrine fibroblast growth factors fgf19, fgf21 and fgf23. Nat Rev Drug Discov,2016,15(1):51-69.
[38] Popescu I R, Helleboid-Chapman A, Lucas A, et al. The nuclear receptor fxr is expressed in pancreatic beta-cells and protects human islets from lipotoxicity. FEBS lett,2010,584(13):2845-2851.
[39] Ghebremariam Y T, Yamada K, Lee J C, et al. Fxr agonist int-747 upregulates ddah expression and enhances insulin sensitivity in high-salt fed dahl rats. Plos One,2013,8(4):e60653.
[40] Seok S, Sun H, Kim Y-C, et al. Defective fxr-shp regulation in obesity aberrantly increases mir-802 expression, promoting insulin resistance and fatty liver. Diabetes,2021,70(3):733-744.
[41] Stofan M, Guo G L. Bile acids and fxr: novel targets for liver diseases. Front Med,2020,7:544.
[42] Hernandez E D, Zheng L, Kim Y, et al. Tropifexor‐mediated abrogation of steatohepatitis and fibrosis is associated with the antioxidative gene expression profile in rodents. Hepatol Commun,2019,3(8):1085-1097.
[43] Sanyal A J, Lopez P, Lawitz E J, et al. Tropifexor for nonalcoholic steatohepatitis: an adaptive, randomized, placebo-controlled phase 2a/b trial. Nat Med,2023,29(2):392-400.
[44] Hollenback D, Hambruch E, Fink G, et al. Development of cilofexor, an intestinally-biased farnesoid x receptor agonist, for the treatment of fatty liver disease. J Pharmacol Exp Ther,2024,389(1):61-75.
[45] Younis I R, Kirby B J, Billin A N, et al.Pharmacokinetics, pharmacodynamics, safety and tolerability of cilofexor, a novel nonsteroidal farnesoid x receptor agonist, in healthy volunteers. Clin Transl Sci,2023,16(3):536-547.
[46] Klucher K, Wang Y, Halcomb R, et al. Fri-313-a novel farnesoid x receptor agonist, tern-101, reduces liver steatosis, inflammation, ballooning and fibrosis in a murine model of non-alcoholic steatohepatitis. J Hepatol,2019,70(1):e534.
[47] 赵欢欢,崔吉,张锦佳,等. 基于法尼醇X受体探讨中医药治疗非酒精性脂肪性肝病的研究进展. 中国中药杂志,2023,48(24):6582-6591.
[48] 章常华,程子文,薛亚楠,等. 葛根芩连汤含药血清对游离脂肪酸诱导的HepG2细胞脂肪堆积模型FXR通路相关信号因子的影响. 时珍国医国药,2022,33(9):2077-2080.
[49] 崔佳斌,郑栋栋,陈奇,等. 二陈汤对非酒精性脂肪性肝病FXR信号通路及胆汁酸水平的影响. 浙江中医杂志,2023,58(2):85-87.
[50] 杨磊,李莹,王炳予,等. 基于法尼醇X受体探讨益气健脾汤对非酒精性脂肪性肝病小鼠糖脂代谢的影响. 中华中医药杂志,2021,36(11):6705-6709.
[51] 田国燕,顾磊,杨劲. 白藜芦醇对小鼠非酒精性脂肪性肝炎相关肝细胞癌的治疗作用及机制研究. 浙江医学,2020,42(3):209-214+303.
[52] Henry Z, Meadows V, Guo G L. Fxr and nash: an avenue for tissue-specific regulation. Hepatol Commun,2023,7(5):e0127.
[53] Li F, Jiang C, Krausz K W, et al. Microbiome remodelling leads to inhibition of intestinal farnesoid x receptor signalling and decreased obesity. Nat Commun,2013,4:2384.

Foles of bile acid FXR receptor on glycolipid metabolism in non-alcoholic fatty liver disease

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