Farnesoid X Receptor Agonists as Therapeutic Target for Cardiometabolic Diseases

被引:39
作者
Li, Chao [1 ]
Yang, Jie [2 ]
Wang, Yu [2 ]
Qi, Yingzi [3 ]
Yang, Wenqing [1 ]
Li, Yunlun [1 ,2 ]
机构
[1] Shandong Univ Tradit Chinese Med, Expt Ctr, Jinan, Peoples R China
[2] Shandong Univ Tradit Chinese Med, Cardiovasc Dept, Affiliated Hosp, Jinan, Peoples R China
[3] Shandong Univ Tradit Chinese Med, Sch Hlth, Jinan, Peoples R China
基金
中国博士后科学基金;
关键词
Farnesoid X Receptor; cardiometabolic diseases; lipid metabolism; diabetes mellitus; obesity; FATTY LIVER-DISEASE; ENDOPLASMIC-RETICULUM STRESS; BILE-ACID METABOLISM; FXR AGONIST; CARDIOVASCULAR-DISEASE; NUCLEAR RECEPTOR; INSULIN-RESISTANCE; CHENODEOXYCHOLIC ACID; OBETICHOLIC ACID; ASYMMETRIC DIMETHYLARGININE;
D O I
10.3389/fphar.2020.01247
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Cardiometabolic diseases are characterized as a combination of multiple risk factors for cardiovascular disease (CVD) and metabolic diseases including diabetes mellitus and dyslipidemia. Cardiometabolic diseases are closely associated with cell glucose and lipid metabolism, inflammatory response and mitochondrial function. Farnesoid X Receptor (FXR), a metabolic nuclear receptor, are found to be activated by primary BAs such as chenodeoxycholic acid (CDCA), cholic acid (CA) and synthetic agonists such as obeticholic acid (OCA). FXR plays crucial roles in regulating cholesterol homeostasis, lipid metabolism, glucose metabolism, and intestinal microorganism. Recently, emerging evidence suggests that FXR agonists are functional for metabolic syndrome and cardiovascular diseases and are considered as a potential therapeutic agent. This review will discuss the pathological mechanism of cardiometabolic disease and reviews the potential mechanisms of FXR agonists in the treatment of cardiometabolic disease.
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页数:15
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共 172 条
  • [1] Intrahepatic Cholestasis of Pregnancy Levels of Sulfated Progesterone Metabolites Inhibit Farnesoid X Receptor Resulting in a Cholestatic Phenotype
    Abu-Hayyeh, Shadi
    Papacleovoulou, Georgia
    Lovgren-Sandblom, Anita
    Tahir, Mehreen
    Oduwole, Olayiwola
    Jamaludin, Nurul Akmal
    Ravat, Sabiha
    Nikolova, Vanya
    Chambers, Jenny
    Selden, Clare
    Rees, Myrddin
    Marschall, Hanns-Ulrich
    Parker, Malcolm G.
    Williamson, Catherine
    [J]. HEPATOLOGY, 2013, 57 (02) : 716 - 726
  • [2] Non-alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases
    Adams, Leon A.
    Anstee, Quentin M.
    Tilg, Herbert
    Targher, Giovanni
    [J]. GUT, 2017, 66 (06) : 1138 - 1153
  • [3] Conformationally constrained farnesoid X receptor (FXR) agonists: Naphthoic acid-based analogs of GW 4064
    Akwabi-Ameyaw, Adwoa
    Bass, Jonathan Y.
    Caldwell, Richard D.
    Caravella, Justin A.
    Chen, Lihong
    Creech, Katrina L.
    Deaton, David N.
    Jones, Stacey A.
    Kaldor, Istvan
    Liu, Yaping
    Madauss, Kevin P.
    Marr, Harry B.
    McFadyen, Robert B.
    Miller, Aaron B.
    Navas, Frank, III
    Parks, Derek J.
    Spearing, Paul K.
    Todd, Dan
    Williams, Shawn P.
    Wisely, G. Bruce
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2008, 18 (15) : 4339 - 4343
  • [4] An FXR Agonist Reduces Bile Acid Synthesis Independently of Increases in FGF19 in Healthy Volunteers
    Al-Khaifi, Amani
    Rudling, Mats
    Angelin, Bo
    [J]. GASTROENTEROLOGY, 2018, 155 (04) : 1012 - 1016
  • [5] A novel non-bile acid FXR agonist EDP-305 potently suppresses liver injury and fibrosis without worsening of ductular reaction
    An, Ping
    Wei, Guangyan
    Huang, Pinzhu
    Li, Wenda
    Qi, Xiaolong
    Lin, Yi
    Vaid, Kahini A.
    Wang, Jun
    Zhang, Shucha
    Li, Yang
    Or, Yat Sun
    Jiang, Li-Juan
    Popov, Yury V.
    [J]. LIVER INTERNATIONAL, 2020, 40 (07) : 1655 - 1669
  • [6] Mechanisms driving the ageing heart
    Anderson, Rhys
    Richardson, Gavin D.
    Passos, Joao F.
    [J]. EXPERIMENTAL GERONTOLOGY, 2018, 109 : 5 - 15
  • [7] Arnett DK, 2019, CIRCULATION, V140, pE563, DOI [10.1016/j.jacc.2019.03.010, 10.1161/CIR.0000000000000677, 10.1161/CIR.0000000000000678, 10.1016/j.jacc.2019.03.009]
  • [8] Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Novel Non-Bile Acid FXR Agonist Tropifexor (LJN452) in Healthy Volunteers
    Badman, Michael K.
    Chen, Jin
    Desai, Sachin
    Vaidya, Soniya
    Neelakantham, Srikanth
    Zhang, Jie
    Gan, Lu
    Danis, Kate
    Laffitte, Bryan
    Klickstein, Lloyd B.
    [J]. CLINICAL PHARMACOLOGY IN DRUG DEVELOPMENT, 2020, 9 (03): : 395 - 410
  • [9] Dual Farnesoid X Receptor/TGR5 Agonist INT-767 Reduces Liver Injury in the Mdr2-/- (Abcb4-/-) Mouse Cholangiopathy Model by Promoting Biliary HCO3- Output
    Baghdasaryan, Anna
    Claudel, Thierry
    Gumhold, Judith
    Silbert, Dagmar
    Adorini, Luciano
    Roda, Aldo
    Vecchiotti, Stefania
    Gonzalez, Frank J.
    Schoonjans, Kristina
    Strazzabosco, Mario
    Fickert, Peter
    Trauner, Michael
    [J]. HEPATOLOGY, 2011, 54 (04) : 1303 - 1312
  • [10] Conformationally constrained farnesoid X receptor (FXR) agonists: Heteroaryl replacements of the naphthalene
    Bass, Jonathan Y.
    Caravella, Justin A.
    Chen, Lihong
    Creech, Katrina L.
    Deaton, David N.
    Madauss, Kevin P.
    Marr, Harry B.
    McFadyen, Robert B.
    Miller, Aaron B.
    Mills, Wendy Y.
    Navas, Frank, III
    Parks, Derek J.
    Smalley, Terrence L., Jr.
    Spearing, Paul K.
    Todd, Dan
    Williams, Shawn P.
    Wisely, G. Bruce
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2011, 21 (04) : 1206 - 1213