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

来源：

FRONTIERS IN PHARMACOLOGY | 2020年 / 11卷

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.

引用

页数：15

共 172 条

[1] Intrahepatic Cholestasis of Pregnancy Levels of Sulfated Progesterone Metabolites Inhibit Farnesoid X Receptor Resulting in a Cholestatic Phenotype [J].

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 .

HEPATOLOGY, 2013, 57 (02) :716-726

[2] Non-alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases [J].

Adams, Leon A. ;

Anstee, Quentin M. ;

Tilg, Herbert ;

Targher, Giovanni .

GUT, 2017, 66 (06) :1138-1153

[3] Conformationally constrained farnesoid X receptor (FXR) agonists: Naphthoic acid-based analogs of GW 4064 [J].

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 .

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 [J].

Al-Khaifi, Amani ;

Rudling, Mats ;

Angelin, Bo .

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 [J].

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. .

LIVER INTERNATIONAL, 2020, 40 (07) :1655-1669

[6] Mechanisms driving the ageing heart [J].

Anderson, Rhys ;

Richardson, Gavin D. ;

Passos, Joao F. .

EXPERIMENTAL GERONTOLOGY, 2018, 109 :5-15

[7]

Arnett DK, 2019, CIRCULATION, V140, pE563, DOI [10.1161/CIR.0000000000000677, 10.1016/j.jacc.2019.03.009, 10.1161/CIR.0000000000000678, 10.1016/j.jacc.2019.03.010]

[8] Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Novel Non-Bile Acid FXR Agonist Tropifexor (LJN452) in Healthy Volunteers [J].

Badman, Michael K. ;

Chen, Jin ;

Desai, Sachin ;

Vaidya, Soniya ;

Neelakantham, Srikanth ;

Zhang, Jie ;

Gan, Lu ;

Danis, Kate ;

Laffitte, Bryan ;

Klickstein, Lloyd B. .

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 [J].

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 .

HEPATOLOGY, 2011, 54 (04) :1303-1312

[10] Conformationally constrained farnesoid X receptor (FXR) agonists: Heteroaryl replacements of the naphthalene [J].