The role of fibroblast growth factor 19 in the pathogenesis of nonalcoholic fatty liver disease

被引:2
作者
Chrysavgis, Lampros [1 ]
Giannakodimos, Ilias [2 ]
Chatzigeorgiou, Antonios [1 ]
Tziomalos, Konstantinos [3 ]
Papatheodoridis, George [4 ]
Cholongitas, Evangelos [2 ]
机构
[1] Natl & Kapodistrian Univ Athens, Dept Physiol, Med Sch, Athens, Greece
[2] Natl & Kapodistrian Univ Athens, Dept Internal Med 1, Med Sch, Athens, Greece
[3] Aristotle Univ Thessaloniki, AHEPA Hosp, Med Sch, Propedeut Dept Internal Med 1, Thessaloniki, Greece
[4] Natl & Kapodistrian Univ Athens, Gen Hosp Athens Laiko, Dept Gastroenterol, Med Sch, Athens, Greece
关键词
Nonalcoholic fatty liver disease; bile acids; fibroblast growth factor-19; fatty acid oxidation; lipid metabolism; clinical limitations; BILE-ACID RECEPTOR; GLUCOSE-METABOLISM; HEPATIC STEATOSIS; FGF19; EXPRESSION; STEATOHEPATITIS; ACTIVATION; FGF15/19; PROTEIN; IDENTIFICATION;
D O I
10.1080/17474124.2022.2127408
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Introduction Nonalcoholic fatty liver disease (NAFLD) has emerged as the predominant cause of chronic liver injury worldwide. Bile acids and their receptors are profoundly implicated in the pathogenesis of NAFLD and its progression to nonalcoholic steatohepatitis and cirrhosis. Areas covered We conducted extensive literature search using PubMed database, and we summarized the relevant literature. We provided an overview of the fibroblast growth factor 19 (FGF-19)-farnesoid X receptor (FXR) axis and summarized the latest findings derived from animal and human studies concerning the impact of FGF-19 on NAFLD. Expert opinion FGF-19, a nutritionally regulated endocrine post-prandial hormone, governs bile acid metabolism, lipid oxidation, lipogenesis, and energy homeostasis. As no approved medication for NAFLD exists, FGF-19 seems to be a propitious therapeutic opportunity for NAFLD, since its administration was associated with ameliorated results in hepatic steatosis, liver inflammation and fibrosis. Furthermore, promising results have been derived from clinical trials concerning the beneficial efficacy of FGF-19 on histological findings and laboratory parameters of NAFLD. However, we should bear in mind the pleiotropic effects of FGF-19 on various metabolically active tissues along with its potential tumorigenic reservoir. Further clinical research is required to determine the clinical application of FGF-19-based therapies on NAFLD.
引用
收藏
页码:835 / 849
页数:15
相关论文
共 71 条
[1]   Nonalcoholic steatohepatitis (NASH) cirrhosis: a snapshot of therapeutic agents in clinical development and the optimal design for clinical trials [J].
Aggarwal, Pankaj ;
Noureddin, Mazen ;
Harrison, Stephen ;
Jeannin, Sophie ;
Alkhouri, Naim .
EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2022, 31 (02) :163-172
[2]   Fibroblast growth factor 15/19 (FGF15/19) protects from diet-induced hepatic steatosis: development of an FGF19-based chimeric molecule to promote fatty liver regeneration [J].
Alvarez-Sola, Gloria ;
Uriarte, Iker ;
Ujue Latasa, M. ;
Fernandez-Barrena, Maite G. ;
Urtasun, Raquel ;
Elizalde, Maria ;
Barcena-Varela, Marina ;
Jimenez, Maddalen ;
Chang, Haisul C. ;
Barbero, Roberto ;
Catalan, Victoria ;
Rodriguez, Amaia ;
Fruhbeck, Gema ;
Gallego-Escuredo, Jose M. ;
Gavalda-Navarr, Aleix ;
Villarroya, Francesc ;
Rodriguez-Ortigosa, Carlos M. ;
Corrales, Fernando J. ;
Prieto, Jesus ;
Berraondo, Pedro ;
Berasain, Carmen ;
Avila, Matias A. .
GUT, 2017, 66 (10) :1818-1828
[3]   The anti-obesity effect of FGF19 does not require UCP1-dependent thermogenesis [J].
Antonellis, Patrick J. ;
Droz, Brian A. ;
Cosgrove, Richard ;
O'Farrell, Libbey S. ;
Coskun, Tamer ;
Perfield, James W., III ;
Bauer, Steven ;
Wade, Mark ;
Chouinard, Tara E. ;
Brozinick, Joseph T. ;
Adams, Andrew C. ;
Samms, Ricardo J. .
MOLECULAR METABOLISM, 2019, 30 :131-139
[4]   Fibroblast growth factor 19 regulates skeletal muscle mass and ameliorates muscle wasting in mice [J].
Benoit, Berengere ;
Meugnier, Emmanuelle ;
Castelli, Martina ;
Chanon, Stephanie ;
Vieille-Marchiset, Aurelie ;
Durand, Christine ;
Bendridi, Nadia ;
Pesenti, Sandra ;
Monternier, Pierre-Axel ;
Durieux, Anne-Cecile ;
Freyssenet, Damien ;
Rieusset, Jennifer ;
Lefai, Etienne ;
Vidal, Hubert ;
Ruzzin, Jerome .
NATURE MEDICINE, 2017, 23 (08) :990-+
[5]   Bile Acids Trigger GLP-1 Release Predominantly by Accessing Basolaterally Located G Protein-Coupled Bile Acid Receptors [J].
Brighton, Cheryl A. ;
Rievaj, Juraj ;
Kuhre, Rune E. ;
Glass, Leslie L. ;
Schoonjans, Kristina ;
Holst, Jens J. ;
Gribble, Fiona M. ;
Reimann, Frank .
ENDOCRINOLOGY, 2015, 156 (11) :3961-3970
[6]   PATHOGENESIS OF GALLSTONES [J].
CAREY, MC .
AMERICAN JOURNAL OF SURGERY, 1993, 165 (04) :410-419
[7]   The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases [J].
Chalasani, Naga ;
Younossi, Zobair ;
Lavine, Joel E. ;
Charlton, Michael ;
Cusi, Kenneth ;
Rinella, Mary ;
Harrison, Stephen A. ;
Brunt, Elizabeth M. ;
Sanyal, Arun J. .
HEPATOLOGY, 2018, 67 (01) :328-357
[8]   Identification of a hormonal basis for gallbladder filling [J].
Choi, Mihwa ;
Moschetta, Antonio ;
Bookout, Angie L. ;
Peng, Li ;
Umetani, Michihisa ;
Holmstrom, Sam R. ;
Suino-Powell, Kelly ;
Xu, H. Eric ;
Richardson, James A. ;
Gerard, Robert D. ;
Mangelsdorf, David J. ;
Kliewer, Steven A. .
NATURE MEDICINE, 2006, 12 (11) :1253-1255
[9]  
clinicaltrials, CT2SHOWNCT03912532
[10]  
clinicaltrials, CT2SHOWNCT02443116