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A Dozen Years of Discovery: Insights into the Physiology and Pharmacology of FGF21.

Kliewer SA, Mangelsdorf DJ.

Cell Metab. 2019 Feb 5;29(2):246-253. doi: 10.1016/j.cmet.2019.01.004. Review.


PPARγ-K107 SUMOylation regulates insulin sensitivity but not adiposity in mice.

Katafuchi T, Holland WL, Kollipara RK, Kittler R, Mangelsdorf DJ, Kliewer SA.

Proc Natl Acad Sci U S A. 2018 Nov 27;115(48):12102-12111. doi: 10.1073/pnas.1814522115. Epub 2018 Nov 12.


The Hormone FGF21 Stimulates Water Drinking in Response to Ketogenic Diet and Alcohol.

Song P, Zechner C, Hernandez G, Cánovas J, Xie Y, Sondhi V, Wagner M, Stadlbauer V, Horvath A, Leber B, Hu MC, Moe OW, Mangelsdorf DJ, Kliewer SA.

Cell Metab. 2018 Jun 5;27(6):1338-1347.e4. doi: 10.1016/j.cmet.2018.04.001. Epub 2018 Apr 12.


Methylprednisolone acetate induces, and Δ7-dafachronic acid suppresses, Strongyloides stercoralis hyperinfection in NSG mice.

Patton JB, Bonne-Année S, Deckman J, Hess JA, Torigian A, Nolan TJ, Wang Z, Kliewer SA, Durham AC, Lee JJ, Eberhard ML, Mangelsdorf DJ, Lok JB, Abraham D.

Proc Natl Acad Sci U S A. 2018 Jan 2;115(1):204-209. doi: 10.1073/pnas.1712235114. Epub 2017 Dec 4.


FGF19, FGF21, and an FGFR1/β-Klotho-Activating Antibody Act on the Nervous System to Regulate Body Weight and Glycemia.

Lan T, Morgan DA, Rahmouni K, Sonoda J, Fu X, Burgess SC, Holland WL, Kliewer SA, Mangelsdorf DJ.

Cell Metab. 2017 Nov 7;26(5):709-718.e3. doi: 10.1016/j.cmet.2017.09.005. Epub 2017 Oct 5.


Nuclear receptors: emerging drug targets for parasitic diseases.

Wang Z, Schaffer NE, Kliewer SA, Mangelsdorf DJ.

J Clin Invest. 2017 Apr 3;127(4):1165-1171. doi: 10.1172/JCI88890. Epub 2017 Feb 6. Review.


FGF21 Is an Exocrine Pancreas Secretagogue.

Coate KC, Hernandez G, Thorne CA, Sun S, Le TDV, Vale K, Kliewer SA, Mangelsdorf DJ.

Cell Metab. 2017 Feb 7;25(2):472-480. doi: 10.1016/j.cmet.2016.12.004. Epub 2017 Jan 12.


KLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference.

Schumann G, Liu C, O'Reilly P, Gao H, Song P, Xu B, Ruggeri B, Amin N, Jia T, Preis S, Segura Lepe M, Akira S, Barbieri C, Baumeister S, Cauchi S, Clarke TK, Enroth S, Fischer K, Hällfors J, Harris SE, Hieber S, Hofer E, Hottenga JJ, Johansson Å, Joshi PK, Kaartinen N, Laitinen J, Lemaitre R, Loukola A, Luan J, Lyytikäinen LP, Mangino M, Manichaikul A, Mbarek H, Milaneschi Y, Moayyeri A, Mukamal K, Nelson C, Nettleton J, Partinen E, Rawal R, Robino A, Rose L, Sala C, Satoh T, Schmidt R, Schraut K, Scott R, Smith AV, Starr JM, Teumer A, Trompet S, Uitterlinden AG, Venturini C, Vergnaud AC, Verweij N, Vitart V, Vuckovic D, Wedenoja J, Yengo L, Yu B, Zhang W, Zhao JH, Boomsma DI, Chambers J, Chasman DI, Daniela T, de Geus E, Deary I, Eriksson JG, Esko T, Eulenburg V, Franco OH, Froguel P, Gieger C, Grabe HJ, Gudnason V, Gyllensten U, Harris TB, Hartikainen AL, Heath AC, Hocking L, Hofman A, Huth C, Jarvelin MR, Jukema JW, Kaprio J, Kooner JS, Kutalik Z, Lahti J, Langenberg C, Lehtimäki T, Liu Y, Madden PA, Martin N, Morrison A, Penninx B, Pirastu N, Psaty B, Raitakari O, Ridker P, Rose R, Rotter JI, Samani NJ, Schmidt H, Spector TD, Stott D, Strachan D, Tzoulaki I, van der Harst P, van Duijn CM, Marques-Vidal P, Vollenweider P, Wareham NJ, Whitfield JB, Wilson J, Wolffenbuttel B, Bakalkin G, Evangelou E, Liu Y, Rice KM, Desrivières S, Kliewer SA, Mangelsdorf DJ, Müller CP, Levy D, Elliott P.

Proc Natl Acad Sci U S A. 2016 Dec 13;113(50):14372-14377. Epub 2016 Nov 28.


Impaired 17,20-Lyase Activity in Male Mice Lacking Cytochrome b5 in Leydig Cells.

Sondhi V, Owen BM, Liu J, Chomic R, Kliewer SA, Hughes BA, Arlt W, Mangelsdorf DJ, Auchus RJ.

Mol Endocrinol. 2016 Apr;30(4):469-78. doi: 10.1210/me.2015-1282. Epub 2016 Mar 14.


Prolongevity hormone FGF21 protects against immune senescence by delaying age-related thymic involution.

Youm YH, Horvath TL, Mangelsdorf DJ, Kliewer SA, Dixit VD.

Proc Natl Acad Sci U S A. 2016 Jan 26;113(4):1026-31. doi: 10.1073/pnas.1514511113. Epub 2016 Jan 11.


Regulation of Life Cycle Checkpoints and Developmental Activation of Infective Larvae in Strongyloides stercoralis by Dafachronic Acid.

Albarqi MM, Stoltzfus JD, Pilgrim AA, Nolan TJ, Wang Z, Kliewer SA, Mangelsdorf DJ, Lok JB.

PLoS Pathog. 2016 Jan 4;12(1):e1005358. doi: 10.1371/journal.ppat.1005358. eCollection 2016 Jan.


FGF21 Regulates Sweet and Alcohol Preference.

Talukdar S, Owen BM, Song P, Hernandez G, Zhang Y, Zhou Y, Scott WT, Paratala B, Turner T, Smith A, Bernardo B, Müller CP, Tang H, Mangelsdorf DJ, Goodwin B, Kliewer SA.

Cell Metab. 2016 Feb 9;23(2):344-9. doi: 10.1016/j.cmet.2015.12.008. Epub 2015 Dec 24.


Bile Acids as Hormones: The FXR-FGF15/19 Pathway.

Kliewer SA, Mangelsdorf DJ.

Dig Dis. 2015;33(3):327-31. doi: 10.1159/000371670. Epub 2015 May 27. Review.


Detection of FGF15 in plasma by stable isotope standards and capture by anti-peptide antibodies and targeted mass spectrometry.

Katafuchi T, Esterházy D, Lemoff A, Ding X, Sondhi V, Kliewer SA, Mirzaei H, Mangelsdorf DJ.

Cell Metab. 2015 Jun 2;21(6):898-904. doi: 10.1016/j.cmet.2015.05.004.


Nuclear receptor PXR: discovery of a pharmaceutical anti-target.

Kliewer SA.

J Clin Invest. 2015 Apr;125(4):1388-9. doi: 10.1172/JCI81244. Epub 2015 Apr 1.


The nuclear receptor DAF-12 regulates nutrient metabolism and reproductive growth in nematodes.

Wang Z, Stoltzfus J, You YJ, Ranjit N, Tang H, Xie Y, Lok JB, Mangelsdorf DJ, Kliewer SA.

PLoS Genet. 2015 Mar 16;11(3):e1005027. doi: 10.1371/journal.pgen.1005027. eCollection 2015 Mar.


Glucocorticoids regulate the metabolic hormone FGF21 in a feed-forward loop.

Patel R, Bookout AL, Magomedova L, Owen BM, Consiglio GP, Shimizu M, Zhang Y, Mangelsdorf DJ, Kliewer SA, Cummins CL.

Mol Endocrinol. 2015 Feb;29(2):213-23. doi: 10.1210/me.2014-1259. Epub 2014 Dec 11.


SnapShot: Hormones of the gastrointestinal tract.

Coate KC, Kliewer SA, Mangelsdorf DJ.

Cell. 2014 Dec 4;159(6):1478.e1. doi: 10.1016/j.cell.2014.11.026.


Tissue-specific actions of the metabolic hormones FGF15/19 and FGF21.

Owen BM, Mangelsdorf DJ, Kliewer SA.

Trends Endocrinol Metab. 2015 Jan;26(1):22-9. doi: 10.1016/j.tem.2014.10.002. Epub 2014 Dec 1. Review.


FGF21 acts centrally to induce sympathetic nerve activity, energy expenditure, and weight loss.

Owen BM, Ding X, Morgan DA, Coate KC, Bookout AL, Rahmouni K, Kliewer SA, Mangelsdorf DJ.

Cell Metab. 2014 Oct 7;20(4):670-7. doi: 10.1016/j.cmet.2014.07.012. Epub 2014 Aug 14.


Circulating FGF21 is liver derived and enhances glucose uptake during refeeding and overfeeding.

Markan KR, Naber MC, Ameka MK, Anderegg MD, Mangelsdorf DJ, Kliewer SA, Mohammadi M, Potthoff MJ.

Diabetes. 2014 Dec;63(12):4057-63. doi: 10.2337/db14-0595. Epub 2014 Jul 9.


Structural insights into gene repression by the orphan nuclear receptor SHP.

Zhi X, Zhou XE, He Y, Zechner C, Suino-Powell KM, Kliewer SA, Melcher K, Mangelsdorf DJ, Xu HE.

Proc Natl Acad Sci U S A. 2014 Jan 14;111(2):839-44. doi: 10.1073/pnas.1322827111. Epub 2013 Dec 30. Erratum in: Proc Natl Acad Sci U S A. 2014 Mar 11;111(10):3895.


FGF21 regulates metabolism and circadian behavior by acting on the nervous system.

Bookout AL, de Groot MH, Owen BM, Lee S, Gautron L, Lawrence HL, Ding X, Elmquist JK, Takahashi JS, Mangelsdorf DJ, Kliewer SA.

Nat Med. 2013 Sep;19(9):1147-52. doi: 10.1038/nm.3249. Epub 2013 Aug 11.


FGF21 contributes to neuroendocrine control of female reproduction.

Owen BM, Bookout AL, Ding X, Lin VY, Atkin SD, Gautron L, Kliewer SA, Mangelsdorf DJ.

Nat Med. 2013 Sep;19(9):1153-6. doi: 10.1038/nm.3250. Epub 2013 Aug 11.


Nuclear receptor LRH-1 induces the reproductive neuropeptide kisspeptin in the hypothalamus.

Atkin SD, Owen BM, Bookout AL, Cravo RM, Lee C, Elias CF, Elmquist JK, Kliewer SA, Mangelsdorf DJ.

Mol Endocrinol. 2013 Apr;27(4):598-605. doi: 10.1210/me.2012-1371. Epub 2013 Mar 15.


Metabolic hormone FGF21 is induced in ground squirrels during hibernation but its overexpression is not sufficient to cause torpor.

Nelson BT, Ding X, Boney-Montoya J, Gerard RD, Kliewer SA, Andrews MT.

PLoS One. 2013;8(1):e53574. doi: 10.1371/journal.pone.0053574. Epub 2013 Jan 2.


Colesevelam suppresses hepatic glycogenolysis by TGR5-mediated induction of GLP-1 action in DIO mice.

Potthoff MJ, Potts A, He T, Duarte JA, Taussig R, Mangelsdorf DJ, Kliewer SA, Burgess SC.

Am J Physiol Gastrointest Liver Physiol. 2013 Feb 15;304(4):G371-80. doi: 10.1152/ajpgi.00400.2012. Epub 2012 Dec 20.


The starvation hormone, fibroblast growth factor-21, extends lifespan in mice.

Zhang Y, Xie Y, Berglund ED, Coate KC, He TT, Katafuchi T, Xiao G, Potthoff MJ, Wei W, Wan Y, Yu RT, Evans RM, Kliewer SA, Mangelsdorf DJ.

Elife. 2012 Oct 15;1:e00065. doi: 10.7554/eLife.00065.


Nuclear receptors HNF4α and LRH-1 cooperate in regulating Cyp7a1 in vivo.

Kir S, Zhang Y, Gerard RD, Kliewer SA, Mangelsdorf DJ.

J Biol Chem. 2012 Nov 30;287(49):41334-41. doi: 10.1074/jbc.M112.421834. Epub 2012 Oct 4.


βKlotho is required for fibroblast growth factor 21 effects on growth and metabolism.

Ding X, Boney-Montoya J, Owen BM, Bookout AL, Coate KC, Mangelsdorf DJ, Kliewer SA.

Cell Metab. 2012 Sep 5;16(3):387-93. doi: 10.1016/j.cmet.2012.08.002.


Liver LXRα expression is crucial for whole body cholesterol homeostasis and reverse cholesterol transport in mice.

Zhang Y, Breevoort SR, Angdisen J, Fu M, Schmidt DR, Holmstrom SR, Kliewer SA, Mangelsdorf DJ, Schulman IG.

J Clin Invest. 2012 May;122(5):1688-99. doi: 10.1172/JCI59817. Epub 2012 Apr 9.


Fibroblast growth factor 21 promotes bone loss by potentiating the effects of peroxisome proliferator-activated receptor γ.

Wei W, Dutchak PA, Wang X, Ding X, Wang X, Bookout AL, Goetz R, Mohammadi M, Gerard RD, Dechow PC, Mangelsdorf DJ, Kliewer SA, Wan Y.

Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):3143-8. doi: 10.1073/pnas.1200797109. Epub 2012 Feb 6.


Fibroblast growth factor-21 regulates PPARγ activity and the antidiabetic actions of thiazolidinediones.

Dutchak PA, Katafuchi T, Bookout AL, Choi JH, Yu RT, Mangelsdorf DJ, Kliewer SA.

Cell. 2012 Feb 3;148(3):556-67. doi: 10.1016/j.cell.2011.11.062.


Endocrine fibroblast growth factors 15/19 and 21: from feast to famine.

Potthoff MJ, Kliewer SA, Mangelsdorf DJ.

Genes Dev. 2012 Feb 15;26(4):312-24. doi: 10.1101/gad.184788.111. Epub 2012 Feb 2. Review.


Structural conservation of ligand binding reveals a bile acid-like signaling pathway in nematodes.

Zhi X, Zhou XE, Melcher K, Motola DL, Gelmedin V, Hawdon J, Kliewer SA, Mangelsdorf DJ, Xu HE.

J Biol Chem. 2012 Feb 10;287(7):4894-903. doi: 10.1074/jbc.M111.315242. Epub 2011 Dec 14.


LRH-1 and PTF1-L coregulate an exocrine pancreas-specific transcriptional network for digestive function.

Holmstrom SR, Deering T, Swift GH, Poelwijk FJ, Mangelsdorf DJ, Kliewer SA, MacDonald RJ.

Genes Dev. 2011 Aug 15;25(16):1674-9. doi: 10.1101/gad.16860911.


Roles of FGF19 in liver metabolism.

Kir S, Kliewer SA, Mangelsdorf DJ.

Cold Spring Harb Symp Quant Biol. 2011;76:139-44. doi: 10.1101/sqb.2011.76.010710. Epub 2011 Aug 3. Review.


FGF15/19 regulates hepatic glucose metabolism by inhibiting the CREB-PGC-1α pathway.

Potthoff MJ, Boney-Montoya J, Choi M, He T, Sunny NE, Satapati S, Suino-Powell K, Xu HE, Gerard RD, Finck BN, Burgess SC, Mangelsdorf DJ, Kliewer SA.

Cell Metab. 2011 Jun 8;13(6):729-38. doi: 10.1016/j.cmet.2011.03.019.


The G protein-coupled bile acid receptor, TGR5, stimulates gallbladder filling.

Li T, Holmstrom SR, Kir S, Umetani M, Schmidt DR, Kliewer SA, Mangelsdorf DJ.

Mol Endocrinol. 2011 Jun;25(6):1066-71. doi: 10.1210/me.2010-0460. Epub 2011 Mar 31.


FGF19 as a postprandial, insulin-independent activator of hepatic protein and glycogen synthesis.

Kir S, Beddow SA, Samuel VT, Miller P, Previs SF, Suino-Powell K, Xu HE, Shulman GI, Kliewer SA, Mangelsdorf DJ.

Science. 2011 Mar 25;331(6024):1621-4. doi: 10.1126/science.1198363.


AKR1B7 is induced by the farnesoid X receptor and metabolizes bile acids.

Schmidt DR, Schmidt S, Holmstrom SR, Makishima M, Yu RT, Cummins CL, Mangelsdorf DJ, Kliewer SA.

J Biol Chem. 2011 Jan 28;286(4):2425-32. doi: 10.1074/jbc.M110.181230. Epub 2010 Nov 16.


Research resource: Comprehensive expression atlas of the fibroblast growth factor system in adult mouse.

Fon Tacer K, Bookout AL, Ding X, Kurosu H, John GB, Wang L, Goetz R, Mohammadi M, Kuro-o M, Mangelsdorf DJ, Kliewer SA.

Mol Endocrinol. 2010 Oct;24(10):2050-64. doi: 10.1210/me.2010-0142. Epub 2010 Jul 28.


Regulation of bile acid synthesis by fat-soluble vitamins A and D.

Schmidt DR, Holmstrom SR, Fon Tacer K, Bookout AL, Kliewer SA, Mangelsdorf DJ.

J Biol Chem. 2010 May 7;285(19):14486-94. doi: 10.1074/jbc.M110.116004. Epub 2010 Mar 16.


Fibroblast growth factor 21: from pharmacology to physiology.

Kliewer SA, Mangelsdorf DJ.

Am J Clin Nutr. 2010 Jan;91(1):254S-257S. doi: 10.3945/ajcn.2009.28449B. Epub 2009 Nov 11. Review.


Chronic diarrhea due to excessive bile acid synthesis and not defective ileal transport: a new syndrome of defective fibroblast growth factor 19 release.

Hofmann AF, Mangelsdorf DJ, Kliewer SA.

Clin Gastroenterol Hepatol. 2009 Nov;7(11):1151-4. doi: 10.1016/j.cgh.2009.07.026. Epub 2009 Aug 7. No abstract available.


FGF21 induces PGC-1alpha and regulates carbohydrate and fatty acid metabolism during the adaptive starvation response.

Potthoff MJ, Inagaki T, Satapati S, Ding X, He T, Goetz R, Mohammadi M, Finck BN, Mangelsdorf DJ, Kliewer SA, Burgess SC.

Proc Natl Acad Sci U S A. 2009 Jun 30;106(26):10853-8. doi: 10.1073/pnas.0904187106. Epub 2009 Jun 16.


Identification of the nuclear receptor DAF-12 as a therapeutic target in parasitic nematodes.

Wang Z, Zhou XE, Motola DL, Gao X, Suino-Powell K, Conneely A, Ogata C, Sharma KK, Auchus RJ, Lok JB, Hawdon JM, Kliewer SA, Xu HE, Mangelsdorf DJ.

Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9138-43. doi: 10.1073/pnas.0904064106. Epub 2009 Jun 2.


MicroRNA let-7 regulates 3T3-L1 adipogenesis.

Sun T, Fu M, Bookout AL, Kliewer SA, Mangelsdorf DJ.

Mol Endocrinol. 2009 Jun;23(6):925-31. doi: 10.1210/me.2008-0298. Epub 2009 Mar 26. Erratum in: Mol Endocrinol. 2009 Sep;23(9):1522.


Structural basis of human pregnane X receptor activation by the hops constituent colupulone.

Teotico DG, Bischof JJ, Peng L, Kliewer SA, Redinbo MR.

Mol Pharmacol. 2008 Dec;74(6):1512-20. doi: 10.1124/mol.108.050732. Epub 2008 Sep 2.


Inhibition of growth hormone signaling by the fasting-induced hormone FGF21.

Inagaki T, Lin VY, Goetz R, Mohammadi M, Mangelsdorf DJ, Kliewer SA.

Cell Metab. 2008 Jul;8(1):77-83. doi: 10.1016/j.cmet.2008.05.006.

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