{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T14:56:39Z","timestamp":1793372199416,"version":"4.5.0"},"reference-count":148,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T00:00:00Z","timestamp":1671580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    As an endocrine hormone, fibroblast growth factor 21 (FGF21) plays a crucial role in regulating lipid, glucose, and energy metabolism. Endogenous FGF21 is generated by multiple cell types but acts on restricted effector tissues, including the brain, adipose tissue, liver, heart, and skeletal muscle. Intervention with FGF21 in rodents or non-human primates has shown significant pharmacological effects on a range of metabolic dysfunctions, including weight loss and improvement of hyperglycemia, hyperlipidemia, insulin resistance, cardiovascular disease, and non-alcoholic fatty liver disease (NAFLD). Due to the poor pharmacokinetic and biophysical characteristics of native FGF21, long-acting FGF21 analogs and FGF21 receptor agonists have been developed for the treatment of metabolic dysfunction. Clinical trials of several FGF21-based drugs have been performed and shown good safety, tolerance, and efficacy. Here we review the actions of FGF21 and summarize the associated clinical trials in obesity, type 2 diabetes mellitus (T2DM), and NAFLD, to help understand and promote the development of efficient treatment for metabolic diseases\n                    <jats:italic>via<\/jats:italic>\n                    targeting FGF21.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2022.1089214","type":"journal-article","created":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T23:44:38Z","timestamp":1671579878000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":73,"title":["The potential function and clinical application of FGF21 in metabolic diseases"],"prefix":"10.3389","volume":"13","author":[{"given":"Zhiwei","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiyong","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,12,21]]},"reference":[{"key":"B1","unstructured":"Pegozafermin (BIO89-100) phase 1b\/2a NASH histology cohort topline results"},{"key":"B2","unstructured":"Reports positive topline results from an expansion cohort of the phase 1b\/2a trial of pegozafermin (BIO89-100) for the treatment of NASH"},{"key":"B3","doi-asserted-by":"publisher","first-page":"106335","DOI":"10.1016\/j.cct.2021.106335","article-title":"The FALCON program: Two phase 2b randomized, double-blind, placebo-controlled studies to assess the efficacy and safety of pegbelfermin in the treatment of patients with nonalcoholic steatohepatitis and bridging fibrosis or compensated cirrhosis","volume":"104","author":"Abdelmalek","year":"2021","journal-title":"Contemp. Clin. Trials."},{"key":"B4","doi-asserted-by":"publisher","first-page":"e65763","DOI":"10.1371\/journal.pone.0065763","article-title":"LY2405319, an engineered FGF21 variant, improves the metabolic status of diabetic monkeys","volume":"8","author":"Adams","year":"2013","journal-title":"PLoS One"},{"key":"B5","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/0306-9877(86)90137-4","article-title":"Bile acid-induced liver toxicity: Relation to the hydrophobic-hydrophilic balance of bile acids","volume":"19","author":"Attili","year":"1986","journal-title":"Med. Hypotheses."},{"key":"B6","doi-asserted-by":"publisher","first-page":"4931","DOI":"10.1210\/en.2009-0532","article-title":"Fibroblast growth factor 21-deficient mice demonstrate impaired adaptation to ketosis","volume":"150","author":"Badman","year":"2009","journal-title":"Endocrinology"},{"key":"B7","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1016\/j.cmet.2007.05.002","article-title":"Hepatic fibroblast growth factor 21 is regulated by PPARalpha and is a key mediator of hepatic lipid metabolism in ketotic states","volume":"5","author":"Badman","year":"2007","journal-title":"Cell Metab."},{"key":"B8","doi-asserted-by":"publisher","first-page":"3379","DOI":"10.1111\/bph.14383","article-title":"A long-acting FGF21 alleviates hepatic steatosis and inflammation in a mouse model of non-alcoholic steatohepatitis partly through an FGF21-adiponectin-IL17A pathway","volume":"175","author":"Bao","year":"2018","journal-title":"Br. J. Pharmacol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1486","DOI":"10.1074\/jbc.M006246200","article-title":"Peroxisome proliferator-activated receptor alpha activates transcription of the Brown fat uncoupling protein-1 gene. A link between regulation of the thermogenic and lipid oxidation pathways in the Brown fat cell","volume":"276","author":"Barbera","year":"2001","journal-title":"J. Biol. Chem."},{"key":"B10","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1038\/nm.2297","article-title":"Brown adipose tissue activity controls triglyceride clearance","volume":"17","author":"Bartelt","year":"2011","journal-title":"Nat. Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"28992","DOI":"10.1073\/pnas.2012073117","article-title":"Antibody-mediated activation of the FGFR1\/Klotho\u03b2 complex corrects metabolic dysfunction and alters food preference in obese humans","volume":"117","author":"Baruch","year":"2020","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B12","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1038\/nrd2792","article-title":"The FGF family: Biology, pathophysiology and therapy","volume":"8","author":"Beenken","year":"2009","journal-title":"Nat. Rev. Drug Discov."},{"key":"B13","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1016\/j.cmet.2017.03.005","article-title":"FGF21 regulates metabolism through adipose-dependent and -independent mechanisms","volume":"25","author":"Bondurant","year":"2017","journal-title":"Cell Metab."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1038\/nm.3249","article-title":"FGF21 regulates metabolism and circadian behavior by acting on the nervous system","volume":"19","author":"Bookout","year":"2013","journal-title":"Nat. Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1046\/j.1523-1755.2001.00781.x","article-title":"Fibroblast growth factor receptors and their ligands in the adult rat kidney","volume":"60","author":"Cancilla","year":"2001","journal-title":"Kidney Int."},{"key":"B16","doi-asserted-by":"publisher","first-page":"2025","DOI":"10.1046\/j.1523-1755.1999.00781.x","article-title":"Expression and localization of fibroblast growth factors and fibroblast growth factor receptors in the developing rat kidney","volume":"56","author":"Cancilla","year":"1999","journal-title":"Kidney Int."},{"key":"B17","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1152\/physrev.00015.2003","article-title":"Brown adipose tissue: Function and physiological significance","volume":"84","author":"Cannon","year":"2004","journal-title":"Physiol. Rev."},{"key":"B18","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1002\/oby.22344","article-title":"Pegbelfermin (BMS\u2010986036), PEGylated FGF21, in patients with obesity and type 2 diabetes: Results from a randomized phase 2 study","volume":"27","author":"Charles","year":"2019","journal-title":"Obes. (Silver Spring, Md"},{"key":"B19","doi-asserted-by":"publisher","first-page":"736","DOI":"10.2119\/molmed.2011.00075","article-title":"Brown adipose tissue responds to cold and adrenergic stimulation by induction of FGF21","volume":"17","author":"Chartoumpekis","year":"2011","journal-title":"Mol. Med."},{"key":"B20","doi-asserted-by":"publisher","first-page":"12553","DOI":"10.1073\/pnas.1006962107","article-title":"Fibroblast growth factor 21 regulates energy metabolism by activating the AMPK-SIRT1-PGC-1alpha pathway","volume":"107","author":"Chau","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B21","doi-asserted-by":"publisher","first-page":"tkac005","DOI":"10.1093\/burnst\/tkac005","article-title":"Roles of the fibroblast growth factor signal transduction system in tissue injury repair","volume":"10","author":"Chen","year":"2022","journal-title":"Burns Trauma"},{"key":"B22","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1530\/JOE-17-0727","article-title":"FGF21 acts as a negative regulator of bile acid synthesis","volume":"237","author":"Chen","year":"2018","journal-title":"J. Endocrinol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"6018","DOI":"10.1210\/en.2008-0816","article-title":"Fibroblast growth factor 21 corrects obesity in mice","volume":"149","author":"Coskun","year":"2008","journal-title":"Endocrinology"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1611","DOI":"10.2337\/db20-0209","article-title":"The effects of B1344, a novel fibroblast growth factor 21 analog, on nonalcoholic steatohepatitis in nonhuman primates","volume":"69","author":"Cui","year":"2020","journal-title":"Diabetes"},{"key":"B25","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1113\/JP275075","article-title":"Restoration of metabolic health by decreased consumption of branched-chain amino acids","volume":"596","author":"Cummings","year":"2018","journal-title":"J. Physiol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"e94996","DOI":"10.1371\/journal.pone.0094996","article-title":"Glucagon stimulates hepatic FGF21 secretion through a PKA- and EPAC-dependent posttranscriptional mechanism","volume":"9","author":"Cyphert","year":"2014","journal-title":"PLoS One"},{"key":"B27","doi-asserted-by":"publisher","first-page":"25123","DOI":"10.1074\/jbc.M112.375907","article-title":"Activation of the farnesoid X receptor induces hepatic expression and secretion of fibroblast growth factor 21","volume":"287","author":"Cyphert","year":"2012","journal-title":"J. Biol. Chem."},{"key":"B28","doi-asserted-by":"publisher","first-page":"140","DOI":"10.2337\/db19-140-lb","article-title":"140-LB: NGM313, a novel activator of b-klotho\/FGFR1c, improves insulin resistance and reduces hepatic fat in obese, nondiabetic subjects","volume":"68","author":"Depaoli","year":"2019","journal-title":"Diabetes"},{"key":"B29","doi-asserted-by":"publisher","first-page":"4238","DOI":"10.1210\/en.2012-1193","article-title":"TNF-Alpha represses beta-klotho expression and impairs FGF21 action in adipose cells: Involvement of JNK1 in the FGF21 pathway","volume":"153","author":"Diaz-Delfin","year":"2012","journal-title":"Endocrinology"},{"key":"B30","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1016\/j.cell.2011.11.062","article-title":"Fibroblast growth factor-21 regulates PPAR\u03b3 activity and the antidiabetic actions of thiazolidinediones","volume":"148","author":"Dutchak","year":"2012","journal-title":"Cell"},{"key":"B31","doi-asserted-by":"publisher","first-page":"4601","DOI":"10.1172\/JCI83349","article-title":"FGF21 and the late adaptive response to starvation in humans","volume":"125","author":"Fazeli","year":"2015","journal-title":"J. Clin. Invest."},{"key":"B32","doi-asserted-by":"publisher","first-page":"2781","DOI":"10.2337\/db10-0193","article-title":"Obesity is a fibroblast growth factor 21 (FGF21)-resistant state","volume":"59","author":"Fisher","year":"2010","journal-title":"Diabetes"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1053\/j.gastro.2014.07.044","article-title":"Fibroblast growth factor 21 limits lipotoxicity by promoting hepatic fatty acid activation in mice on methionine and choline-deficient diets","volume":"147","author":"Fisher","year":"2014","journal-title":"Gastroenterology"},{"key":"B34","doi-asserted-by":"publisher","first-page":"2996","DOI":"10.1210\/en.2011-0281","article-title":"Integrated regulation of hepatic metabolism by fibroblast growth factor 21 (FGF21) in vivo","volume":"152","author":"Fisher","year":"2011","journal-title":"Endocrinology"},{"key":"B35","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.molmet.2016.11.008","article-title":"A critical role for ChREBP-mediated FGF21 secretion in hepatic fructose metabolism","volume":"6","author":"Fisher","year":"2017","journal-title":"Mol. Metab."},{"key":"B36","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1101\/gad.177857.111","article-title":"FGF21 regulates PGC-1\u03b1 and browning of white adipose tissues in adaptive thermogenesis","volume":"26","author":"Fisher","year":"2012","journal-title":"Gene. Dev."},{"key":"B37","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1038\/s42255-021-00354-2","article-title":"Metabolic messengers: FGF21","volume":"3","author":"Flippo","year":"2021","journal-title":"Nat. Metab."},{"key":"B38","doi-asserted-by":"publisher","first-page":"162ra153","DOI":"10.1126\/scitranslmed.3004690","article-title":"Treating diabetes and obesity with an FGF21-mimetic antibody activating the \u03b2Klotho\/FGFR1c receptor complex","volume":"4","author":"Foltz","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"B39","doi-asserted-by":"publisher","first-page":"2050","DOI":"10.1210\/me.2010-0142","article-title":"Research resource: Comprehensive expression atlas of the fibroblast growth factor system in adult mouse","volume":"24","author":"Fon Tacer","year":"2010","journal-title":"Mol. Endocrinol. Baltim. Md"},{"key":"B40","doi-asserted-by":"publisher","first-page":"4130","DOI":"10.1128\/MCB.00596-14","article-title":"MicroRNA 34a inhibits beige and Brown fat formation in obesity in part by suppressing adipocyte fibroblast growth factor 21 signaling and SIRT1 function","volume":"34","author":"Fu","year":"2014","journal-title":"Mol. Cell. Biol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1016\/j.cmet.2013.08.005","article-title":"The effects of LY2405319, an FGF21 analog, in obese human subjects with type 2 diabetes","volume":"18","author":"Gaich","year":"2013","journal-title":"Cell Metab."},{"key":"B42","doi-asserted-by":"publisher","first-page":"13717","DOI":"10.1038\/srep13717","article-title":"Fibroblast growth factor 21 in breast milk controls neonatal intestine function","volume":"5","author":"Gavalda-Navarro","year":"2015","journal-title":"Sci. Rep."},{"key":"B43","doi-asserted-by":"publisher","first-page":"4169","DOI":"10.3390\/nu14194169","article-title":"Do sugar-sweetened beverages increase fasting FGF21 irrespective of the type of added sugar? A secondary exploratory analysis of a randomized controlled trial","volume":"14","author":"Geidl-Flueck","year":"2022","journal-title":"Nutrients"},{"key":"B44","doi-asserted-by":"publisher","first-page":"2738","DOI":"10.1016\/j.celrep.2019.02.014","article-title":"Exercise alleviates obesity-induced metabolic dysfunction via enhancing FGF21 sensitivity in adipose tissues","volume":"26","author":"Geng","year":"2019","journal-title":"Cell Rep."},{"key":"B45","doi-asserted-by":"publisher","first-page":"3417","DOI":"10.1128\/MCB.02249-06","article-title":"Molecular insights into the klotho-dependent, endocrine mode of action of fibroblast growth factor 19 subfamily members","volume":"27","author":"Goetz","year":"2007","journal-title":"Mol. Cell. Biol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1016\/j.molmet.2015.06.001","article-title":"Glucagon-to-insulin ratio is pivotal for splanchnic regulation of FGF-21 in humans","volume":"4","author":"Hansen","year":"2015","journal-title":"Mol. Metab."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1262","DOI":"10.1038\/s41591-021-01425-3","article-title":"Efruxifermin in non-alcoholic steatohepatitis: A randomized, double-blind, placebo-controlled, phase 2a trial","volume":"27","author":"Harrison","year":"2021","journal-title":"Nat. Med."},{"key":"B48","doi-asserted-by":"publisher","first-page":"6758","DOI":"10.1038\/sj.onc.1209943","article-title":"NF-kappaB and the immune response","volume":"25","author":"Hayden","year":"2006","journal-title":"Oncogene"},{"key":"B49","doi-asserted-by":"publisher","first-page":"2934","DOI":"10.1016\/j.celrep.2019.05.022","article-title":"FGF21 signals protein status to the brain and adaptively regulates food choice and metabolism","volume":"27","author":"Hill","year":"2019","journal-title":"Cell Rep."},{"key":"B50","doi-asserted-by":"publisher","first-page":"12983","DOI":"10.1074\/jbc.M110.215889","article-title":"Thermogenic activation induces FGF21 expression and release in Brown adipose tissue","volume":"286","author":"Hondares","year":"2011","journal-title":"J. Biol. Chem."},{"key":"B51","doi-asserted-by":"publisher","first-page":"2382","DOI":"10.1016\/j.peptides.2007.10.007","article-title":"The fasting polypeptide FGF21 can enter brain from blood","volume":"28","author":"Hsuchou","year":"2007","journal-title":"Peptides"},{"key":"B52","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1093\/jmcb\/mjw013","article-title":"The FGF21-adiponectin axis in controlling energy and vascular homeostasis","volume":"8","author":"Hui","year":"2016","journal-title":"J. Mol. Cell Biol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1016\/j.cmet.2007.05.003","article-title":"Endocrine regulation of the fasting response by PPARalpha-mediated induction of fibroblast growth factor 21","volume":"5","author":"Inagaki","year":"2007","journal-title":"Cell Metab."},{"key":"B54","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/s0925-4773(00)00439-1","article-title":"Molecular cloning and expression analyses of mouse betaklotho, which encodes a novel Klotho family protein","volume":"98","author":"Ito","year":"2000","journal-title":"Mech. Dev."},{"key":"B55","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1093\/jb\/mvq121","article-title":"Fibroblast growth factors: From molecular evolution to roles in development, metabolism and disease","volume":"149","author":"Itoh","year":"2011","journal-title":"J. Biochem."},{"key":"B56","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/j.cmet.2020.06.008","article-title":"FGF21 signals to glutamatergic neurons in the ventromedial hypothalamus to suppress carbohydrate intake","volume":"32","author":"Jensen-Cody","year":"2020","journal-title":"Cell Metab."},{"key":"B57","doi-asserted-by":"publisher","first-page":"29751","DOI":"10.1074\/jbc.M114.565960","article-title":"Fibroblast growth factor 21 is regulated by the IRE1\u03b1-XBP1 branch of the unfolded protein response and counteracts endoplasmic reticulum stress-induced hepatic steatosis","volume":"289","author":"Jiang","year":"2014","journal-title":"J. Biol. Chem."},{"key":"B58","doi-asserted-by":"publisher","first-page":"e8791","DOI":"10.15252\/emmm.201708791","article-title":"FGF21 gene therapy as treatment for obesity and insulin resistance","volume":"10","author":"Jimenez","year":"2018","journal-title":"EMBO Mol. Med."},{"key":"B59","doi-asserted-by":"publisher","first-page":"E916","DOI":"10.1152\/ajpendo.00559.2013","article-title":"Silencing of the Fibroblast growth factor 21 gene is an underlying cause of acinar cell injury in mice lacking MIST1","volume":"306","author":"Johnson","year":"2014","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"B60","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.1053\/j.gastro.2009.07.064","article-title":"Fibroblast growth factor 21 reduces the severity of cerulein-induced pancreatitis in mice","volume":"137","author":"Johnson","year":"2009","journal-title":"Gastroenterology"},{"key":"B61","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.bbrc.2015.02.081","article-title":"FGF21 attenuates pathological myocardial remodeling following myocardial infarction through the adiponectin-dependent mechanism","volume":"459","author":"Joki","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B62","doi-asserted-by":"publisher","first-page":"100057","DOI":"10.1016\/j.xcrm.2020.100057","article-title":"AKR-001, an fc-FGF21 analog, showed sustained pharmacodynamic effects on insulin sensitivity and lipid metabolism in type 2 diabetes patients","volume":"1","author":"Kaufman","year":"2020","journal-title":"Cell Rep. Med."},{"key":"B63","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1016\/j.molmet.2015.04.006","article-title":"Genetic disruption of uncoupling protein 1 in mice renders Brown adipose tissue a significant source of FGF21 secretion","volume":"4","author":"Keipert","year":"2015","journal-title":"Mol. Metab."},{"key":"B64","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1038\/s41467-019-14069-2","article-title":"Endogenous FGF21-signaling controls paradoxical obesity resistance of UCP1-deficient mice","volume":"11","author":"Keipert","year":"2020","journal-title":"Nat. Commun."},{"key":"B65","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/j.molmet.2013.12.003","article-title":"Inventing new medicines: The FGF21 story","volume":"3","author":"Kharitonenkov","year":"2014","journal-title":"Mol. Metab."},{"key":"B66","doi-asserted-by":"publisher","first-page":"e58575","DOI":"10.1371\/journal.pone.0058575","article-title":"Rational design of a fibroblast growth factor 21-based clinical candidate, LY2405319","volume":"8","author":"Kharitonenkov","year":"2013","journal-title":"PLoS One"},{"key":"B67","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.1172\/JCI23606","article-title":"FGF-21 as a novel metabolic regulator","volume":"115","author":"Kharitonenkov","year":"2005","journal-title":"J. Clin. Invest."},{"key":"B68","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1210\/en.2006-1168","article-title":"The metabolic state of diabetic monkeys is regulated by fibroblast growth factor-21","volume":"148","author":"Kharitonenkov","year":"2007","journal-title":"Endocrinology"},{"key":"B69","doi-asserted-by":"publisher","first-page":"1762","DOI":"10.1111\/dom.13023","article-title":"Once-weekly administration of a long-acting fibroblast growth factor 21 analogue modulates lipids, bone turnover markers, blood pressure and body weight differently in obese people with hypertriglyceridaemia and in non-human primates","volume":"19","author":"Kim","year":"2017","journal-title":"Diabetes Obes. Metab."},{"key":"B70","doi-asserted-by":"publisher","first-page":"3366","DOI":"10.1210\/en.2012-2276","article-title":"Fibroblast growth factor 21 improves insulin resistance and ameliorates renal injury in db\/db mice","volume":"154","author":"Kim","year":"2013","journal-title":"Endocrinology"},{"key":"B71","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1007\/s00125-014-3475-6","article-title":"Fibroblast growth factor 21 participates in adaptation to endoplasmic reticulum stress and attenuates obesity-induced hepatic metabolic stress","volume":"58","author":"Kim","year":"2014","journal-title":"Diabetologia"},{"key":"B72","doi-asserted-by":"publisher","first-page":"26687","DOI":"10.1074\/jbc.M704165200","article-title":"Tissue-specific expression of betaKlotho and fibroblast growth factor (FGF) receptor isoforms determines metabolic activity of FGF19 and FGF21","volume":"282","author":"Kurosu","year":"2007","journal-title":"J. Biol. Chem."},{"key":"B73","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.1016\/j.celrep.2015.10.021","article-title":"FGF21-Mediated improvements in glucose clearance require uncoupling protein 1","volume":"13","author":"Kwon","year":"2015","journal-title":"Cell Rep."},{"key":"B74","doi-asserted-by":"publisher","first-page":"155329","DOI":"10.1016\/j.metabol.2022.155329","article-title":"Genome-wide association and Mendelian randomization study of fibroblast growth factor 21 reveals causal associations with hyperlipidemia and possibly NASH","volume":"137","author":"Larsson","year":"2022","journal-title":"Metabolism"},{"key":"B75","doi-asserted-by":"publisher","first-page":"e0192146","DOI":"10.1371\/journal.pone.0192146","article-title":"LY2405319, an analog of fibroblast growth factor 21 ameliorates alpha-smooth muscle actin production through inhibition of the succinate-G-protein couple receptor 91 (GPR91) pathway in mice","volume":"13","author":"Le","year":"2018","journal-title":"PLoS One"},{"key":"B76","first-page":"4750","article-title":"An engineered FGF21 variant, LY2405319, can prevent non-alcoholic steatohepatitis by enhancing hepatic mitochondrial function","volume":"8","author":"Lee","year":"2016","journal-title":"Am. J. Transl. Res."},{"key":"B77","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1016\/j.metabol.2012.01.012","article-title":"Fibroblast growth factor-21 protects human skeletal muscle myotubes from palmitate-induced insulin resistance by inhibiting stress kinase and NF-\u03baB","volume":"61","author":"Lee","year":"2012","journal-title":"Metabolism"},{"key":"B78","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1038\/nature25010","article-title":"Structures of beta-klotho reveal a 'zip code'-like mechanism for endocrine FGF signalling","volume":"553","author":"Lee","year":"2018","journal-title":"Nature"},{"key":"B79","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1007\/s11684-019-0711-y","article-title":"The FGF metabolic axis","volume":"13","author":"Li","year":"2019","journal-title":"Front. Med."},{"key":"B80","doi-asserted-by":"publisher","first-page":"4064","DOI":"10.2337\/db14-0541","article-title":"FGF21 maintains glucose homeostasis by mediating the cross talk between liver and brain during prolonged fasting","volume":"63","author":"Liang","year":"2014","journal-title":"Diabetes"},{"key":"B81","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1016\/j.cmet.2013.04.005","article-title":"Adiponectin mediates the metabolic effects of FGF21 on glucose homeostasis and insulin sensitivity in mice","volume":"17","author":"Lin","year":"2013","journal-title":"Cell Metab."},{"key":"B82","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1093\/cvr\/cvab076","article-title":"Pharmacological treatment with FGF21 strongly improves plasma cholesterol metabolism to reduce atherosclerosis","volume":"118","author":"Liu","year":"2022","journal-title":"Cardiovasc. Res."},{"key":"B83","first-page":"1011","article-title":"Lack of fibroblast growth factor 21 accelerates metabolic liver injury characterized by steatohepatities in mice","volume":"6","author":"Liu","year":"2016","journal-title":"Am. J. Cancer Res."},{"key":"B84","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1016\/j.bbrc.2007.06.068","article-title":"PPARalpha is a key regulator of hepatic FGF21","volume":"360","author":"Lundasen","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B85","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.molmet.2016.11.001","article-title":"Circulating FGF21 in humans is potently induced by short term overfeeding of carbohydrates","volume":"6","author":"Lundsgaard","year":"2017","journal-title":"Mol. Metab."},{"key":"B86","doi-asserted-by":"publisher","first-page":"100392","DOI":"10.1016\/j.jhepr.2021.100392","article-title":"Pegbelfermin selectively reduces secondary bile acid concentrations in patients with non-alcoholic steatohepatitis","volume":"4","author":"Luo","year":"2022","journal-title":"JHEP Rep."},{"key":"B87","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/2193-1801-3-2","article-title":"Fibroblast growth factor-21 enhances mitochondrial functions and increases the activity of PGC-1\u03b1 in human dopaminergic neurons via Sirtuin-1","volume":"3","author":"Makela","year":"2014","journal-title":"Springerplus"},{"key":"B88","doi-asserted-by":"publisher","first-page":"4057","DOI":"10.2337\/db14-0595","article-title":"Circulating FGF21 is liver derived and enhances glucose uptake during refeeding and overfeeding","volume":"63","author":"Markan","year":"2014","journal-title":"Diabetes"},{"key":"B89","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.semcdb.2015.09.021","article-title":"Metabolic fibroblast growth factors (FGFs): Mediators of energy homeostasis","volume":"53","author":"Markan","year":"2016","journal-title":"Semin. Cell Dev. Biol."},{"key":"B90","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1002\/dmrr.1177","article-title":"Direct effects of FGF21 on glucose uptake in human skeletal muscle: Implications for type 2 diabetes and obesity","volume":"27","author":"Mashili","year":"2011","journal-title":"Diabetes Metab. Res. Rev."},{"key":"B91","doi-asserted-by":"publisher","first-page":"804","DOI":"10.3748\/wjg.15.804","article-title":"Bile acids: Chemistry, physiology, and pathophysiology","volume":"15","author":"Monte","year":"2009","journal-title":"World J. Gastroenterol."},{"key":"B92","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1053\/j.gastro.2013.05.042","article-title":"Efficacy and safety of the farnesoid X receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease","volume":"145","author":"Mudaliar","year":"2013","journal-title":"Gastroenterology"},{"key":"B93","doi-asserted-by":"publisher","first-page":"3691","DOI":"10.1172\/JCI77508","article-title":"Play down protein to play up metabolism?","volume":"124","author":"Muller","year":"2014","journal-title":"J. Clin. investigation"},{"key":"B94","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/s0167-4781(00)00067-1","article-title":"Identification of a novel FGF, FGF-21, preferentially expressed in the liver","volume":"1492","author":"Nishimura","year":"2000","journal-title":"Biochim. Biophys. Acta"},{"key":"B95","doi-asserted-by":"publisher","first-page":"7432","DOI":"10.1073\/pnas.0701600104","article-title":"BetaKlotho is required for metabolic activity of fibroblast growth factor 21","volume":"104","author":"Ogawa","year":"2007","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B96","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1016\/j.bbrc.2011.07.125","article-title":"Time-imposed daily restricted feeding induces rhythmic expression of Fgf21 in white adipose tissue of mice","volume":"412","author":"Oishi","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B97","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1016\/j.cmet.2011.06.012","article-title":"Different metabolic responses of human Brown adipose tissue to activation by cold and insulin","volume":"14","author":"Orava","year":"2011","journal-title":"Cell Metab."},{"key":"B98","doi-asserted-by":"publisher","first-page":"1153","DOI":"10.1038\/nm.3250","article-title":"FGF21 contributes to neuroendocrine control of female reproduction","volume":"19","author":"Owen","year":"2013","journal-title":"Nat. Med."},{"key":"B99","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1172\/JCI123069","article-title":"Adipocyte-secreted exosomal microRNA-34a inhibits M2 macrophage polarization to promote obesity-induced adipose inflammation","volume":"129","author":"Pan","year":"2019","journal-title":"J. Clin. Invest."},{"key":"B100","doi-asserted-by":"publisher","first-page":"e87102","DOI":"10.1371\/journal.pone.0087102","article-title":"Novel insights into the cardio-protective effects of FGF21 in lean and obese rat hearts","volume":"9","author":"Patel","year":"2014","journal-title":"PLoS One"},{"key":"B101","doi-asserted-by":"publisher","first-page":"2019","DOI":"10.1038\/ncomms3019","article-title":"Fibroblast growth factor 21 protects against cardiac hypertrophy in mice","volume":"4","author":"Planavila","year":"2013","journal-title":"Nat. Commun."},{"key":"B102","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1093\/cvr\/cvu263","article-title":"Fibroblast growth factor 21 protects the heart from oxidative stress","volume":"106","author":"Planavila","year":"2015","journal-title":"Cardiovasc. Res."},{"key":"B103","doi-asserted-by":"publisher","first-page":"10853","DOI":"10.1073\/pnas.0904187106","article-title":"FGF21 induces PGC-1alpha and regulates carbohydrate and fatty acid metabolism during the adaptive starvation response","volume":"106","author":"Potthoff","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B104","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1530\/JME-19-0210","article-title":"Fibroblast growth factor-21 potentiates glucose transport in skeletal muscle fibers","volume":"65","author":"Rosales-Soto","year":"2020","journal-title":"J. Mol. Endocrinol."},{"key":"B105","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.cell.2013.12.012","article-title":"What we talk about when we talk about fat","volume":"156","author":"Rosen","year":"2014","journal-title":"Cell"},{"key":"B106","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1016\/j.celrep.2015.04.046","article-title":"Discrete aspects of FGF21 in vivo Pharmacology do not require UCP1","volume":"11","author":"Samms","year":"2015","journal-title":"Cell Rep."},{"key":"B107","doi-asserted-by":"publisher","first-page":"2705","DOI":"10.1016\/S0140-6736(18)31785-9","article-title":"Pegbelfermin (BMS-986036), a PEGylated fibroblast growth factor 21 analogue, in patients with non-alcoholic steatohepatitis: A randomised, double-blind, placebo-controlled, phase 2a trial","volume":"392","author":"Sanyal","year":"2019","journal-title":"Lancet"},{"key":"B108","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1016\/j.cmet.2016.01.006","article-title":"FGF21 lowers plasma triglycerides by accelerating lipoprotein catabolism in white and Brown adipose tissues","volume":"23","author":"Schlein","year":"2016","journal-title":"Cell Metab."},{"key":"B109","doi-asserted-by":"publisher","first-page":"G440","DOI":"10.1152\/ajpgi.00322.2009","article-title":"The hepatic response to FGF19 is impaired in patients with nonalcoholic fatty liver disease and insulin resistance","volume":"298","author":"Schreuder","year":"2010","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"B110","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1016\/j.molmet.2016.05.010","article-title":"Fibroblast growth factor 21 has no direct role in regulating fertility in female mice","volume":"5","author":"Singhal","year":"","journal-title":"Mol. Metab."},{"key":"B111","doi-asserted-by":"publisher","first-page":"e0148252","DOI":"10.1371\/journal.pone.0148252","article-title":"Fibroblast growth factor 21 (FGF21) protects against high fat diet induced inflammation and islet hyperplasia in pancreas","volume":"11","author":"Singhal","year":"","journal-title":"PLoS One"},{"key":"B112","doi-asserted-by":"publisher","first-page":"e61432","DOI":"10.1371\/journal.pone.0061432","article-title":"FGF21 can be mimicked in vitro and in vivo by a novel anti-FGFR1c\/\u03b2-Klotho bispecific protein","volume":"8","author":"Smith","year":"2013","journal-title":"PLoS One"},{"key":"B113","doi-asserted-by":"publisher","first-page":"3751","DOI":"10.2337\/db13-0645","article-title":"High glucose represses beta-klotho expression and impairs fibroblast growth factor 21 action in mouse pancreatic islets: Involvement of peroxisome proliferator-activated receptor gamma signaling","volume":"62","author":"So","year":"2013","journal-title":"Diabetes"},{"key":"B114","doi-asserted-by":"publisher","first-page":"802541","DOI":"10.3389\/fendo.2021.802541","article-title":"The nuanced metabolic functions of endogenous FGF21 depend on the nature of the stimulus, tissue source, and experimental model","volume":"12","author":"Spann","year":"2021","journal-title":"Front. Endocrinol. (Lausanne)"},{"key":"B115","doi-asserted-by":"publisher","first-page":"1314","DOI":"10.1210\/en.2016-1917","article-title":"A novel fc-FGF21 with improved resistance to proteolysis, increased affinity toward beta-klotho, and enhanced efficacy in mice and cynomolgus monkeys","volume":"158","author":"Stanislaus","year":"2017","journal-title":"Endocrinology"},{"key":"B116","doi-asserted-by":"publisher","first-page":"5928","DOI":"10.7150\/ijbs.76924","article-title":"Hepatic FGF21: Its emerging role in inter-organ crosstalk and cancers","volume":"18","author":"Sui","year":"2022","journal-title":"Int. J. Biol. Sci."},{"key":"B117","doi-asserted-by":"publisher","first-page":"11841","DOI":"10.1038\/s41598-019-48356-1","article-title":"Activation of cardiac AMPK-FGF21 feed-forward loop in acute myocardial infarction: Role of adrenergic overdrive and lipolysis byproducts","volume":"9","author":"Sunaga","year":"2019","journal-title":"Sci. Rep."},{"key":"B118","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1210\/me.2007-0313","article-title":"betaKlotho is required for fibroblast growth factor (FGF) 21 signaling through FGF receptor (FGFR) 1c and FGFR3c","volume":"22","author":"Suzuki","year":"2008","journal-title":"Mol. Endocrinol."},{"key":"B119","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1055\/a-1778-4159","article-title":"FGF21: A novel regulator of glucose and lipid metabolism and whole-body energy balance","volume":"54","author":"Szczepa\u0144ska","year":"2022","journal-title":"Horm. Metab. Res."},{"key":"B120","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1016\/j.cmet.2015.12.008","article-title":"FGF21 regulates sweet and alcohol preference","volume":"23","author":"Talukdar","year":"","journal-title":"Cell Metab."},{"key":"B121","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1016\/j.cmet.2016.02.001","article-title":"A long-acting FGF21 molecule, PF-05231023, decreases body weight and improves lipid profile in non-human primates and type 2 diabetic subjects","volume":"23","author":"Talukdar","year":"","journal-title":"Cell Metab."},{"key":"B122","doi-asserted-by":"publisher","first-page":"1242","DOI":"10.1016\/j.bbadis.2015.02.012","article-title":"Role of fibroblast growth factor 21 in the early stage of NASH induced by methionine- and choline-deficient diet","volume":"1852","author":"Tanaka","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"B123","doi-asserted-by":"publisher","first-page":"4552","DOI":"10.7150\/thno.24723","article-title":"Liver-heart crosstalk controls IL-22 activity in cardiac protection after myocardial infarction","volume":"8","author":"Tang","year":"2018","journal-title":"Theranostics"},{"key":"B124","doi-asserted-by":"publisher","first-page":"e12828","DOI":"10.14814\/phy2.12828","article-title":"Acute exercise increases fibroblast growth factor 21 in metabolic organs and circulation","volume":"4","author":"Tanimura","year":"2016","journal-title":"Physiol. Rep."},{"key":"B125","doi-asserted-by":"publisher","first-page":"419","DOI":"10.3389\/fphys.2019.00419","article-title":"FGF21 as modulator of metabolism in health and disease","volume":"10","author":"Tezze","year":"2019","journal-title":"Front. Physiol."},{"key":"B126","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1007\/s10928-016-9481-1","article-title":"PF-05231023, a long-acting FGF21 analogue, decreases body weight by reduction of food intake in non-human primates","volume":"43","author":"Thompson","year":"2016","journal-title":"J. Pharmacokinet. Phar."},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1007\/s10741-022-10268-0","article-title":"Fibroblast growth factor 21 in heart failure","author":"Tucker","year":"2022","journal-title":"Heart fail. Rev"},{"key":"B128","doi-asserted-by":"publisher","first-page":"247","DOI":"10.4161\/isl.2.4.12402","article-title":"FGF-21 enhances islet engraftment in mouse syngeneic islet transplantation model","volume":"2","author":"Uonaga","year":"2010","journal-title":"Islets"},{"key":"B129","doi-asserted-by":"publisher","first-page":"e2210434119","DOI":"10.1073\/pnas.2210434119","article-title":"Phosphorylation of RXR\u03b1 mediates the effect of JNK to suppress hepatic FGF21 expression and promote metabolic syndrome","volume":"119","author":"Vernia","year":"2022","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B130","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/j.cmet.2015.12.003","article-title":"FGF21 mediates endocrine control of simple sugar intake and sweet taste preference by the liver","volume":"23","author":"von Holstein-Rathlou","year":"2016","journal-title":"Cell Metab."},{"key":"B131","doi-asserted-by":"publisher","first-page":"4702","DOI":"10.1007\/s12035-017-0663-7","article-title":"FGF21 attenuates high-fat diet-induced cognitive impairment via metabolic regulation and anti-inflammation of obese mice","volume":"55","author":"Wang","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"B132","doi-asserted-by":"publisher","first-page":"3143","DOI":"10.1073\/pnas.1200797109","article-title":"Fibroblast growth factor 21 promotes bone loss by potentiating the effects of peroxisome proliferator-activated receptor \u03b3","volume":"109","author":"Wei","year":"2012","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B133","doi-asserted-by":"publisher","first-page":"e0119104","DOI":"10.1371\/journal.pone.0119104","article-title":"Pharmacokinetics (PK), pharmacodynamics (PD) and integrated PK\/PD modeling of a novel long acting FGF21 clinical candidate PF-05231023 in diet-induced obese and leptin-deficient obese mice","volume":"10","author":"Weng","year":"2015","journal-title":"PLoS One"},{"key":"B134","doi-asserted-by":"publisher","first-page":"2470","DOI":"10.2337\/db05-1435","article-title":"Fibroblast growth factor-21 improves pancreatic beta-cell function and survival by activation of extracellular signal-regulated kinase 1\/2 and Akt signaling pathways","volume":"55","author":"Wente","year":"2006","journal-title":"Diabetes"},{"key":"B135","doi-asserted-by":"publisher","DOI":"10.1002\/hep.32742","article-title":"Fibroblast growth factor receptor 1\/klotho\u03b2 agonist BFKB8488A improves lipids and liver health markers in patients with diabetes or NAFLD: A phase 1b randomized trial","author":"Wong","year":"2022","journal-title":"Hepatology"},{"key":"B136","doi-asserted-by":"publisher","first-page":"E1105","DOI":"10.1152\/ajpendo.00348.2009","article-title":"Acute glucose-lowering and insulin-sensitizing action of FGF21 in insulin-resistant mouse models--association with liver and adipose tissue effects","volume":"297","author":"Xu","year":"2009","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"B137","doi-asserted-by":"publisher","first-page":"e33870","DOI":"10.1371\/journal.pone.0033870","article-title":"Differential specificity of endocrine FGF19 and FGF21 to FGFR1 and FGFR4 in complex with KLB","volume":"7","author":"Yang","year":"2012","journal-title":"PLoS One"},{"key":"B138","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1530\/EC-19-0034","article-title":"Exercise ameliorates the FGF21-adiponectin axis impairment in diet-induced obese mice","volume":"8","author":"Yang","year":"2019","journal-title":"Endocr. Connect."},{"key":"B139","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1186\/1472-6882-12-156","article-title":"Inhibition by curcumin of multiple sites of the transforming growth factor-beta1 signalling pathway ameliorates the progression of liver fibrosis induced by carbon tetrachloride in rats","volume":"12","author":"Yao","year":"2012","journal-title":"BMC Complement. Altern. Med."},{"key":"B140","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1002\/hep.27060","article-title":"Fibroblast growth factor 21 protects against acetaminophen-induced hepatotoxicity by potentiating peroxisome proliferator-activated receptor coactivator protein-1\u03b1-mediated antioxidant capacity in mice","volume":"60","author":"Ye","year":"2014","journal-title":"Hepatology"},{"key":"B141","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1111\/j.1747-0285.2012.01325.x","article-title":"Understanding the physical interactions in the FGF21\/FGFR\/\u03b2-Klotho complex: Structural requirements and implications in FGF21 signaling","volume":"79","author":"Yie","year":"2012","journal-title":"Chem. Biol. Drug Des."},{"key":"B142","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/j.biochi.2018.05.020","article-title":"Enhanced expression and distinctive characterization of a long-acting FGF21 and its potential to alleviate nonalcoholic steatohepatitis","volume":"151","author":"Yin","year":"2018","journal-title":"Biochimie"},{"key":"B143","doi-asserted-by":"publisher","first-page":"2672","DOI":"10.1002\/hep.30251","article-title":"Global perspectives on nonalcoholic fatty liver disease and nonalcoholic steatohepatitis","volume":"69","author":"Younossi","year":"2019","journal-title":"Hepatology"},{"key":"B144","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1007\/s11010-015-2358-6","article-title":"Fibroblast growth factor (FGF21) protects mouse liver against D-galactose-induced oxidative stress and apoptosis via activating Nrf2 and PI3K\/Akt pathways","volume":"403","author":"Yu","year":"2015","journal-title":"Mol. Cell. Biochem."},{"key":"B145","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1111\/liv.13591","article-title":"Complications, symptoms, quality of life and pregnancy in cholestatic liver disease","volume":"38","author":"Zakharia","year":"2018","journal-title":"Liver Int."},{"key":"B146","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/j.molmet.2017.12.008","article-title":"Hepatic regulation of VLDL receptor by PPAR\u03b2\/\u03b4 and FGF21 modulates non-alcoholic fatty liver disease","volume":"8","author":"Zarei","year":"2018","journal-title":"Mol. Metab."},{"key":"B147","doi-asserted-by":"publisher","first-page":"15694","DOI":"10.1074\/jbc.M601252200","article-title":"Receptor specificity of the fibroblast growth factor family. The complete mammalian FGF family","volume":"281","author":"Zhang","year":"2006","journal-title":"J. Biol. Chem."},{"key":"B148","doi-asserted-by":"publisher","first-page":"2931","DOI":"10.1097\/CM9.0000000000001890","article-title":"The role of FGF21 in the pathogenesis of cardiovascular disease","volume":"134","author":"Zhang","year":"2021","journal-title":"Chin. Med. J.-Peking."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.1089214\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T23:44:43Z","timestamp":1671579883000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.1089214\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,21]]},"references-count":148,"alternative-id":["10.3389\/fphar.2022.1089214"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2022.1089214","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,21]]},"article-number":"1089214"}}