Fibroblast growth factor (FGF)-21 based therapies: A magic bullet for nonalcoholic fatty liver disease (NAFLD)?

References

• Younossi ZM, Koenig AB, Abdelatif D, et al. Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;641:73–84. Epub 2015/12/29 PubMed PMID: 26707365
   PubMed Web of Science ®Google Scholar
• Noureddin M, Vipani A, Bresee C, et al. NASH leading cause of liver transplant in women: updated analysis of indications for liver transplant and ethnic and gender variances. Am J Gastroenterol. 2018;113(11):1649–1659. Epub 2018/ 06/09. PubMed PMID: 29880964.
   PubMed Web of Science ®Google Scholar
• Mohamad B, Shah V, Onyshchenko M, et al. Characterization of hepatocellular carcinoma (HCC) in non-alcoholic fatty liver disease (NAFLD) patients without cirrhosis. Hepatol Int. 2016;10(4):632–639. Epub 2015/ 11/13. PubMed PMID: 26558795.
   PubMed Web of Science ®Google Scholar
• Shetty A, Syn WK. Health and economic burden of nonalcoholic fatty liver disease in the United States and its impact on veterans. Fed Pract. 2019;36(1): 14–19. Epub 2019/02/16. PubMed PMID: 30766413; PubMed Central PMCID: PMCPMC6366581 interest with regard to this article.
   PubMedGoogle Scholar
• BonDurant LD, Ameka M, Naber MC, et al. FGF21 regulates metabolism through adipose-dependent and -independent mechanisms. Cell Metab. 2017;25(4):935–44 e4. Epub 2017/04/06.PubMed PMID: 28380381; PubMed Central PMCID: PMCPMC5494834.
   PubMed Web of Science ®Google Scholar
• Giralt M, Gavalda-Navarro A, Villarroya F. Fibroblast growth factor-21, energy balance and obesity. Mol Cell Endocrinol. 2015;418Pt 1:66–73. Epub 2015/09/30. PubMed PMID: 26415590.
   PubMedGoogle Scholar
• Lin Z, Tian H, Lam KS, et al. Adiponectin mediates the metabolic effects of FGF21 on glucose homeostasis and insulin sensitivity in mice. Cell Metab. 2013;17(5):779–789. Epub 2013/05/15. PubMed PMID: 23663741.
   PubMed Web of Science ®Google Scholar
• Mulder P, Morrison MC, Verschuren L, et al. Reduction of obesity-associated white adipose tissue inflammation by rosiglitazone is associated with reduced non-alcoholic fatty liver disease in LDLr-deficient mice. Sci Rep. 2016;6:31542. Epub 2016/08/23. PubMed PMID: 27545964; PubMed Central PMCID: PMCPMC4992869.
   PubMed Web of Science ®Google Scholar
• Dolegowska K, Marchelek-Mysliwiec M, Nowosiad-Magda M, et al. FGF19 subfamily members: FGF19 and FGF21. J Physiol Biochem. 2019;75(2): 229–240. Epub 2019/ 03/31. 10.1007/s13105-019-00675-7. PubMed PMID: 30927227; PubMed Central PMCID: PMCPMC6611749.
   PubMed Web of Science ®Google Scholar
• Zhang F, Yu L, Lin X, et al. Minireview: roles of fibroblast growth factors 19 and 21 in metabolic regulation and chronic diseases. Mol Endocrinol. 2015;29(10):1400–1413. Epub 2015/ 08/27.PubMed PMID: 26308386; PubMed Central PMCID: PMCPMC4588730.
   PubMedGoogle Scholar
• Powers CJ, McLeskey SW, Wellstein A. Fibroblast growth factors, their receptors and signaling. Endocr Relat Cancer. 2000;7(3): 165–197. Epub 2000/10/06.PubMed PMID: 11021964.
   PubMed Web of Science ®Google Scholar
• Schlessinger J, Plotnikov AN, Ibrahimi OA, et al. Crystal structure of a ternary FGF-FGFR-heparin complex reveals a dual role for heparin in FGFR binding and dimerization. Mol Cell. 2000;6(3):743–750. Epub 2000/10/13. PubMed PMID: 11030354.
   PubMed Web of Science ®Google Scholar
• Kurosu H, Choi M, Ogawa Y, et al. Tissue-specific expression of betaKlotho and fibroblast growth factor (FGF) receptor isoforms determines metabolic activity of FGF19 and FGF21. J Biol Chem. 2007;282(37):26687–26695. Epub 2007/ 07/12. PubMed PMID: 17623664; PubMed Central PMCID: PMCPMC2496965.
   PubMed Web of Science ®Google Scholar
• Fisher FM, Estall JL, Adams AC, et al. Integrated regulation of hepatic metabolism by fibroblast growth factor 21 (FGF21) in vivo. Endocrinology. 2011;152(8):2996–3004. Epub 2011/ 06/30. PubMed PMID: 21712364; PubMed Central PMCID: PMCPMC3138239.
   PubMed Web of Science ®Google Scholar
• Jiang S, Yan C, Fang QC, et al. Fibroblast growth factor 21 is regulated by the IRE1alpha-XBP1 branch of the unfolded protein response and counteracts endoplasmic reticulum stress-induced hepatic steatosis. J Biol Chem. 2014;289(43):29751–29765. Epub 2014/08/30. PubMed PMID: 25170079; PubMed Central PMCID: PMCPMC4207989.
   PubMed Web of Science ®Google Scholar
• Woolsey SJ, Beaton MD, Mansell SE, et al. A fibroblast growth factor 21-pregnane X receptor pathway downregulates hepatic CYP3A4 in nonalcoholic fatty liver disease. Mol Pharmacol. 2016;90(4):437–446. Epub 2016/08/03. PubMed PMID: 27482056.
   PubMed Web of Science ®Google Scholar
• Fon Tacer K, Bookout AL, Ding X, et al. Research resource: comprehensive expression atlas of the fibroblast growth factor system in adult mouse. Mol Endocrinol. 2010;24(10):2050–2064. Epub 2010/ 07/30. PubMed PMID: 20667984; PubMed Central PMCID: PMCPMC2954642.
   PubMedGoogle Scholar
• Hsuchou H, Pan W, Kastin AJ. The fasting polypeptide FGF21 can enter brain from blood. Peptides. 2007;2812:2382–2386. Epub 2007/11/13. PubMed PMID: 17996984; PubMed Central PMCID: PMCPMC2151924.
   PubMed Web of Science ®Google Scholar
• Bookout AL, de Groot MH, Owen BM, et al. FGF21 regulates metabolism and circadian behavior by acting on the nervous system. Nat Med. 2013;19(9):1147–1152. Epub 2013/08/13. PubMed PMID: 23933984; PubMed Central PMCID: PMCPMC3769420.
   PubMed Web of Science ®Google Scholar
• Lan T, Morgan DA, Rahmouni K, et al. FGF19, FGF21, and an FGFR1/beta-Klotho-activating antibody act on the nervous system to regulate body weight and glycemia. Cell Metab. 2017;26(5):709–18 e3. Epub 2017/10/11. PubMed PMID: 28988823; PubMed Central PMCID: PMCPMC5679468.
   PubMed Web of Science ®Google Scholar
• Owen BM, Ding X, Morgan DA, et al. FGF21 acts centrally to induce sympathetic nerve activity, energy expenditure, and weight loss. Cell Metab. 2014;20(4):670–677. Epub 2014/08/19. PubMed PMID: 25130400; PubMed Central PMCID: PMCPMC4192037.
   PubMed Web of Science ®Google Scholar
• Tezze C, Romanello V, Sandri M. FGF21 as modulator of metabolism in health and disease. Front Physiol. 2019;10:419. Epub 2019/05/07. PubMed PMID: 31057418; PubMed Central PMCID: PMCPMC6478891.
   PubMed Web of Science ®Google Scholar
• Kharitonenkov A, Shiyanova TL, Koester A, et al. FGF-21 as a novel metabolic regulator. J Clin Invest. 2005;115(6):1627–1635. Epub 2005/05/20. PubMed PMID: 15902306; PubMed Central PMCID: PMCPMC1088017.
   PubMed Web of Science ®Google Scholar
• Inagaki T, Lin VY, Goetz R, et al. Inhibition of growth hormone signaling by the fasting-induced hormone FGF21. Cell Metab. 2008;81:77–83. Epub 2008/07/01. PubMed PMID: 18585098; PubMed Central PMCID: PMCPMC2575072.
   PubMed Web of Science ®Google Scholar
• Muise ES, Souza S, Chi A, et al. Downstream signaling pathways in mouse adipose tissues following acute in vivo administration of fibroblast growth factor 21. PloS One. 2013;8(9):e73011. Epub 2013/09/17. PubMed PMID: 24039848; PubMed Central PMCID: PMCPMC3765203.
   PubMed Web of Science ®Google Scholar
• Kim AM, Somayaji VR, Dong JQ, et al. 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. Diabetes Obes Metab. 2017;19(12):1762–1772. Epub 2017/06/03. PubMed PMID: 28573777.
   PubMed Web of Science ®Google Scholar
• Talukdar S, Zhou Y, Li D, et al. A long-acting FGF21 molecule, PF-05231023, decreases body weight and improves lipid profile in non-human primates and type 2 diabetic subjects. Cell Metab. 2016;23(3):427–440. Epub 2016/03/10. PubMed PMID: 26959184.
   PubMed Web of Science ®Google Scholar
• Yamauchi T, Kamon J, Waki H, et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med. 2001;7(8):941–946. Epub 2001/08/02. PubMed PMID: 11479627.
   PubMed Web of Science ®Google Scholar
• Gasser E, Moutos CP, Downes M, et al. FGF1 - a new weapon to control type 2 diabetes mellitus. Nat Rev Endocrinol. 2017;1310:599–609. Epub 2017/07/01. PubMed PMID: 28664920; PubMed Central PMCID: PMCPMC5839646.
   PubMed Web of Science ®Google Scholar
• Badman MK, Pissios P, Kennedy AR, et al. Hepatic fibroblast growth factor 21 is regulated by PPARalpha and is a key mediator of hepatic lipid metabolism in ketotic states. Cell Metab. 2007;56:426–437. Epub 2007/06/07. PubMed PMID: 17550778.
   PubMed Web of Science ®Google Scholar
• Zhang C, Huang Z, Gu J, et al. Fibroblast growth factor 21 protects the heart from apoptosis in a diabetic mouse model via extracellular signal-regulated kinase 1/2-dependent signalling pathway. Diabetologia. 2015;58(8):1937–1948. Epub 2015/06/05. PubMed PMID: 26040473.
   PubMed Web of Science ®Google Scholar
• Lakhani I, Gong M, Wong WT, et al. Fibroblast growth factor 21 in cardio-metabolic disorders: a systematic review and meta-analysis. Metabolism. 2018;83:11–17. Epub 2018/ 02/08. PubMed PMID: 29410351.
   PubMed Web of Science ®Google Scholar
• Hong ES, Lim C, Choi HY, et al. Plasma fibroblast growth factor 21 levels increase with ectopic fat accumulation and its receptor levels are decreased in the visceral fat of patients with type 2 diabetes. BMJ Open Diabetes Res Care. 2019;7(1):e000776. Epub 2019/12/05. PubMed PMID: 31798902; PubMed Central PMCID: PMCPMC6861080.
   PubMed Web of Science ®Google Scholar
• Inagaki T, Dutchak P, Zhao G, et al. Endocrine regulation of the fasting response by PPARalpha-mediated induction of fibroblast growth factor 21. Cell Metab. 2007;5(6):415–425. Epub 2007/06/07. PubMed PMID: 17550777.
   PubMed Web of Science ®Google Scholar
• Wei W, Dutchak PA, Wang X, et al. Fibroblast growth factor 21 promotes bone loss by potentiating the effects of peroxisome proliferator-activated receptor gamma. Proc Natl Acad Sci U S A. 2012;109(8):3143–3148. Epub 2012/02/09. PubMed PMID: 22315431; PubMed Central PMCID: PMCPMC3286969.
   PubMed Web of Science ®Google Scholar
• Popp KL, Turkington V, Hughes JM, et al. Skeletal loading score is associated with bone microarchitecture in young adults. Bone. 2019;127:360–366. Epub 2019/07/03. PubMed PMID: 31265923.
   PubMed Web of Science ®Google Scholar
• Andersen B, Straarup EM, Heppner KM, et al. FGF21 decreases body weight without reducing food intake or bone mineral density in high-fat fed obese rhesus macaque monkeys. Int J Obes (Lond). 2018;42(6):1151–1160. Epub 2018/06/13. PubMed PMID: 29892039; PubMed Central PMCID: PMCPMC6733401.
   PubMed Web of Science ®Google Scholar
• Charles ED, Neuschwander-Tetri BA, Pablo Frias J, et al. Pegbelfermin (BMS-986036), PEGylated FGF21, in patients with obesity and type 2 diabetes: results from a randomized phase 2 study. Obesity (Silver Spring). 2019;27(1):41–49. Epub 2018/ 12/07. PubMed PMID: 30520566; PubMed Central PMCID: PMCPMC6587787.
   PubMed Web of Science ®Google Scholar
• Nielsen MJ, Kazankov K, Leeming DJ, et al. Markers of collagen remodeling detect clinically significant fibrosis in chronic hepatitis C patients. PloS One. 2015;10(9):e0137302. Epub 2015/09/26. PubMed PMID: 26406331; PubMed Central PMCID: PMCPMC4583995.
   PubMed Web of Science ®Google Scholar
• Sanyal A, Charles ED, Neuschwander-Tetri BA, et al. 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. Lancet. 2019;392(10165):2705–2717. Epub 2018/12/18. PubMed PMID: 30554783.
   PubMed Web of Science ®Google Scholar
• Chen MM, Hale C, Stanislaus S, et al. FGF21 acts as a negative regulator of bile acid synthesis. J Endocrinol. 2018;2372:139–152. Epub 2018/04/05. PubMed PMID: 29615519.
   PubMed Web of Science ®Google Scholar
• Stanislaus S, Hecht R, Yie J, et al. A novel Fc-FGF21 with improved resistance to proteolysis, increased affinity toward beta-Klotho, and enhanced efficacy in mice and cynomolgus monkeys. Endocrinology. 2017;158(5):1314–1327. Epub 2017/03/23. PubMed PMID: 28324011.
   PubMed Web of Science ®Google Scholar
• Amgen Clinical Trials. [cited 2020 Jan 7]. Available from: http://wwwamgentrialscom/amgen/studylistaspx?productid=67
   Google Scholar
• Yang C, Jin C, Li X, et al. Differential specificity of endocrine FGF19 and FGF21 to FGFR1 and FGFR4 in complex with KLB. PloS One. 2012;73:e33870. Epub 2012/03/24. PubMed PMID: 22442730; PubMed Central PMCID: PMCPMC3307775.
   PubMed Web of Science ®Google Scholar