Circulating α-klotho regulates metabolism via distinct central and peripheral mechanisms

Kuro-o M. Nabeshima Y. Matsumura Y. Aizawa H. Kawaguchi H. Suga T. et al.

Mutation of the mouse klotho gene leads to a syndrome resembling ageing.

Nature. 390: 45-51https://doi.org/10.1038/36285

H. Kurosu, M. Yamamoto, J.D. Clark, J. V Pastor, A. Nandi, P. Gurnani, O.P. McGuinness, H. Chikuda, M. Yamaguchi, H. Kawaguchi, I. Shimomura, Y. Takayama, J. Herz, C.R. Kahn, K.P. Rosenblatt, M. Kuro-o, Suppression of Aging in Mice by the Hormone Klotho, Science (80-. ). 309 (2005) 1829–1833. doi:https://doi.org/10.1126/science.1112766.

J. Leon, A.J. Moreno, B.I. Garay, R.J. Chalkley, A.L. Burlingame, D. Wang, D.B. Dubal, Peripheral Elevation of a Klotho Fragment Enhances Brain Function and Resilience in Young, Aging, and α-Synuclein Transgenic Mice., Cell Rep. 20 (2017) 1360–1371. doi:https://doi.org/10.1016/j.celrep.2017.07.024.

Baluchnejadmojarad T. Eftekhari S.-M. Jamali-Raeufy N. Haghani S. Zeinali H. Roghani M.

The anti-aging protein klotho alleviates injury of nigrostriatal dopaminergic pathway in 6-hydroxydopamine rat model of Parkinson's disease: involvement of PKA/CaMKII/CREB signaling.

Exp Gerontol. 100: 70-76https://doi.org/10.1016/j.exger.2017.10.023Zeldich E. Chen C.-D. Colvin T.A. Bove-Fenderson E.A. Liang J. Tucker Zhou T.B. et al.

The neuroprotective effect of klotho is mediated via regulation of members of the redox system.

J Biol Chem. 289: 24700-24715Chen C.-D. Sloane J.A. Li H. Aytan N. Giannaris E.L. Zeldich E. et al.

The antiaging protein klotho enhances oligodendrocyte maturation and myelination of the CNS.

J Neurosci. 33: 1927-1939Adeli S. Zahmatkesh M. Tavoosidana G. Karimian M. Hassanzadeh G.

Simvastatin enhances the hippocampal klotho in a rat model of streptozotocin-induced cognitive decline.

Prog Neuro-Psychopharmacology Biol Psychiatry. 72: 87-94https://doi.org/10.1016/j.pnpbp.2016.09.009Rao Z. Landry T. Li P. Bunner W. Laing B.T. Yuan Y. et al.

Administration of alpha klotho reduces liver and adipose lipid accumulation in obese mice.

Heliyon. 5e01494https://doi.org/10.1016/j.heliyon.2019.e01494

In vivo pancreatic β-cell-specific expression of antiaging gene klotho: a novel approach for preserving β-cells in type 2 diabetes.

Diabetes. 64: 1444-1458https://doi.org/10.2337/db14-0632

Antiaging gene klotho enhances glucose-induced insulin secretion by up-regulating plasma membrane levels of TRPV2 in MIN6 β-cells.

Endocrinology. 153: 3029-3039https://doi.org/10.1210/en.2012-1091

Y. Lin, Z. Sun, Antiaging Gene Klotho Attenuates Pancreatic β-Cell Apoptosis in Type 1 Diabetes., Diabetes. 64 (2015) 4298–311. doi:https://doi.org/10.2337/db15-0066.

Mori K. Yahata K. Mukoyama M. Suganami T. Makino H. Nagae T. et al.

Disruption of klotho gene causes an abnormal energy homeostasis in mice.

Biochem Biophys Res Commun. 278: 665-670Prud'homme G.J. Glinka Y. Kurt M. Liu W. Wang Q.

The anti-aging protein klotho is induced by GABA therapy and exerts protective and stimulatory effects on pancreatic beta cells.

Biochem Biophys Res Commun. Prud'homme G.J. Glinka Y. Kurt M. Liu W. Wang Q.

Systemic klotho therapy protects against insulitis and enhances beta-cell mass in NOD mice.

Biochem Biophys Res Commun. https://doi.org/10.1016/j.bbrc.2020.02.123Xing L. Guo H. Meng S. Zhu B. Fang J. Huang J. et al.

Klotho ameliorates diabetic nephropathy by activating Nrf2 signaling pathway in podocytes.

Biochem Biophys Res Commun. https://doi.org/10.1016/j.bbrc.2020.11.061Matsubara T. Miyaki A. Akazawa N. Choi Y. Ra S.-G. Tanahashi K. et al.

Aerobic exercise training increases plasma klotho levels and reduces arterial stiffness in postmenopausal women.

Am J Physiol Circ Physiol. 306: H348-H355https://doi.org/10.1152/ajpheart.00429.2013Semba R.D. Cappola A.R. Sun K. Bandinelli S. Dalal M. Crasto C. et al.

Plasma klotho and cardiovascular disease in adults.

J Am Geriatr Soc. 59: 1596-1601Li X. Li Z. Li B. Zhu X. Lai X.

Klotho improves diabetic cardiomyopathy by suppressing the NLRP3 inflammasome pathway.

Life Sci. 234: 116773https://doi.org/10.1016/J.LFS.2019.116773Chen L.-J. Cheng M.-F. Ku P.-M. Cheng J.-T.

Cerebral klotho protein as a humoral factor for maintenance of Baroreflex.

Horm Metab Res. 47: 125-132https://doi.org/10.1055/s-0034-1375689Kuwahara N. Sasaki S. Kobara M. Nakata T. Tatsumi T. Irie H. et al.

HMG-CoA reductase inhibition improves anti-aging klotho protein expression and arteriosclerosis in rats with chronic inhibition of nitric oxide synthesis.

Int J Cardiol. 123: 84-90https://doi.org/10.1016/j.ijcard.2007.02.029

P. Ravikumar, J. Ye, J. Zhang, S.N. Pinch, M.C. Hu, M. Kuro-o, C.C.W. Hsia, O.W. Moe, α-Klotho protects against oxidative damage in pulmonary epithelia., Am. J. Physiol. Lung Cell. Mol. Physiol. 307 (2014) L566–75.

Rhee E.J. Oh K.W. Lee W.Y. Kim S.Y. Jung C.H. Kim B.J. et al.

The differential effects of age on the association of KLOTHO gene polymorphisms with coronary artery disease.

Metabolism. 55: 1344-1351https://doi.org/10.1016/j.metabol.2006.05.020Imamura A. Okumura K. Ogawa Y. Murakami R. Torigoe M. Numaguchi Y. et al.

Klotho gene polymorphism may be a genetic risk factor for atherosclerotic coronary artery disease but not for vasospastic angina in Japanese.

Clin Chim Acta. 371: 66-70https://doi.org/10.1016/j.cca.2006.02.021Kim Y. Kim J.H. Nam Y.J. Kong M. Kim Y.J. Yu K.H. et al.

Klotho is a genetic risk factor for ischemic stroke caused by cardioembolism in Korean females.

Neurosci Lett. 407: 189-194https://doi.org/10.1016/j.neulet.2006.08.039Arking D.E. Becker D.M. Yanek L.R. Fallin D. Judge D.P. Moy T.F. et al.

KLOTHO allele status and the risk of early-onset occult coronary artery disease.

Am J Hum Genet. 72: 1154-1161https://doi.org/10.1086/375035Tsujikawa H. Kurotaki Y. Fujimori T. Fukuda K. Nabeshima Y.-I.

Klotho, a gene related to a syndrome resembling human premature aging, functions in a negative regulatory circuit of vitamin D endocrine system.

Mol Endocrinol. 17: 2393-2403https://doi.org/10.1210/me.2003-0048

Klotho: a novel regulator of calcium and phosphorus homeostasis.

Pflügers Arch - Eur J Physiol. 462: 185-193https://doi.org/10.1007/s00424-011-0950-5Duce J.A. Podvin S. Hollander W. Kipling D. Rosene D.L. Abraham C.R.

Gene profile analysis implicates klotho as an important contributor to aging changes in brain white matter of the rhesus monkey.

Glia. 56: 106-117https://doi.org/10.1002/glia.20593Nakatani T. Sarraj B. Ohnishi M. Densmore M.J. Taguchi T. Goetz R. et al.

In vivo genetic evidence for klotho-dependent, fibroblast growth factor 23 (Fgf23) -mediated regulation of systemic phosphate homeostasis.

FASEB J. 23: 433-441https://doi.org/10.1096/fj.08-114397Wolf I. Levanon-Cohen S. Bose S. Ligumsky H. Sredni B. Kanety H. et al.

Klotho: a tumor suppressor and a modulator of the IGF-1 and FGF pathways in human breast cancer.

Oncogene. 27: 7094-7105https://doi.org/10.1038/onc.2008.292Hu M.C. Shi M. Zhang J. Addo T. Cho H.J. Barker S.L. et al.

Renal production, uptake, and handling of circulating αklotho.

J Am Soc Nephrol. 27: 79-90https://doi.org/10.1681/ASN.2014101030Matsumura Y. Aizawa H. Shiraki-Iida T. Nagai R. Kuro-O M. Nabeshima Y.I.

Identification of the human klotho gene and its two transcripts encoding membrane and secreted klotho protein.

Biochem Biophys Res Commun. 242: 626-630https://doi.org/10.1006/bbrc.1997.8019Shiraki-Iida T. Aizawa H. Matsumura Y. Sekine S. Iida A. Anazawa H. et al.

Structure of the mouse klotho gene and its two transcripts encoding membrane and secreted protein 1.

FEBS Lett. 424: 6-10https://doi.org/10.1016/S0014-5793(98)00127-6Tohyama O. Imura A. Iwano A. Freund J.N. Henrissat B. Fujimori T. et al.

Klotho is a novel β-Glucuronidase capable of hydrolyzing steroid β-glucuronides.

J Biol Chem. 279: 9777-9784https://doi.org/10.1074/jbc.M312392200Chen C.-D. Podvin S. Gillespie E. Leeman S.E. Abraham C.R.

Insulin stimulates the cleavage and release of the extracellular domain of klotho by ADAM10 and ADAM17.

Proc Natl Acad Sci. 104: 19796-19801https://doi.org/10.1073/pnas.0709805104Imura A. Iwano A. Tohyama O. Tsuji Y. Nozaki K. Hashimoto N. et al.

Secreted klotho protein in sera and CSF: implication for post-translational cleavage in release of klotho protein from cell membrane.

FEBS Lett. 565: 143-147https://doi.org/10.1016/j.febslet.2004.03.090van Loon E.P.M. Pulskens W.P. van der Hagen E.A.E. Lavrijsen M. Vervloet M.G. van Goor H. et al.

Shedding of klotho by ADAMs in the kidney.

Am J Physiol Physiol. 309: F359-F368https://doi.org/10.1152/ajprenal.00240.2014Bloch L. Sineshchekova O. Reichenbach D. Reiss K. Saftig P. Kuro-o M. et al.

Klotho is a substrate for α-, β- and γ-secretase.

FEBS Lett. 583: 3221-3224https://doi.org/10.1016/j.febslet.2009.09.009Mitani H. Ishizaka N. Aizawa T. Ohno M. Usui S. Suzuki T. et al.

In vivo klotho gene transfer ameliorates angiotensin II-induced renal damage.

Hypertension. 39: 838-843https://doi.org/10.1161/01.HYP.0000013734.33441.EAUtsugi T. Ohno T. Ohyama Y. Uchiyama T. Saito Y. Matsumura Y. et al.

Decreased insulin production and increased insulin sensitivity in the klotho mutant mouse, a novel animal model for human aging.

Metabolism. 49: 1118-1123https://doi.org/10.1053/meta.2000.8606Hasannejad M. Samsamshariat S.Z. Esmaili A. Jahanian-Najafabadi A.

Klotho induces insulin resistance possibly through interference with GLUT4 translocation and activation of Akt, GSK3β, and PFKfβ3 in 3T3-L1 adipocyte cells.

Res Pharm Sci. 14: 369-377https://doi.org/10.4103/1735-5362.263627Olauson H. Mencke R. Hillebrands J.-L. Larsson T.E.

Tissue expression and source of circulating αKlotho.

Bone. 100: 19-35https://doi.org/10.1016/j.bone.2017.03.043Zhang H. Li Y. Fan Y. Wu J. Zhao B. Guan Y. et al.

Klotho is a target gene of PPAR-γ.

Kidney Int. 74: 732-739https://doi.org/10.1038/ki.2008.244Chihara Y. Rakugi H. Ishikawa K. Ikushima M. Maekawa Y. Ohta J. et al.

Klotho protein promotes adipocyte differentiation.

Endocrinology. 147: 3835-3842https://doi.org/10.1210/en.2005-1529Öz O.K. Hajibeigi A. Howard K. Cummins C.L. van Abel M. Bindels R.J. et al.

Aromatase deficiency causes altered expression of molecules critical for calcium reabsorption in the kidneys of female mice.

J Bone Miner Res. 22: 1893-1902https://doi.org/10.1359/jbmr.070808Carpenter T.O. Insogna K.L. Zhang J.H. Ellis B. Nieman S. Simpson C. et al.

Circulating levels of soluble klotho and FGF23 in X-linked hypophosphatemia: circadian variance, effects of treatment, and relationship to parathyroid status.

J Clin Endocrinol Metab. 95: E352-E357https://doi.org/10.1210/jc.2010-0589Tan S.-J. Smith E.R. Hewitson T.D. Holt S.G. Toussaint N.D.

Diurnal variation and short-term pre-analytical stability of serum soluble α-klotho in healthy volunteers: a pilot study.

Ann Clin Biochem. 52: 506-509https://doi.org/10.1177/0004563214563415

L. Pedersen, S.M. Pedersen, C.L. Brasen, L.M. Rasmussen, Soluble serum Klotho levels in healthy subjects. Comparison of two different immunoassays, Clin. Biochem. 46 (2013) 1079–1083. doi:https://doi.org/10.1016/j.clinbiochem.2013.05.046.

Yamazaki Y. Imura A. Urakawa I. Shimada T. Murakami J. Aono Y. et al.

Establishment of sandwich ELISA for soluble alpha-klotho measurement: age-dependent change of soluble alpha-klotho levels in healthy subjects.

Biochem Biophys Res Commun. 398: 513-518https://doi.org/10.1016/j.bbrc.2010.06.110Semba R.D. Cappola A.R. Sun K. Bandinelli S. Dalal M. Crasto C. et al.

Plasma klotho and mortality risk in older community-dwelling adults.

J Gerontol A Biol Sci Med Sci. 66: 794-800https://doi.org/10.1093/gerona/glr058Liu F. Wu S. Ren H. Gu J.

Klotho suppresses RIG-I-mediated senescence-associated inflammation.

Nat Cell Biol. 13: 254-262https://doi.org/10.1038/ncb2167

M. Yamamoto, J.D. Clark, J. V Pastor, P. Gurnani, A. Nandi, H. Kurosu, M. Miyoshi, Y. Ogawa, D.H. Castrillon, K.P. Rosenblatt, M. Kuro-O, Regulation of Oxidative Stress by the Anti-aging Hormone Klotho * ࡗ, (2005). doi:https://doi.org/10.1074/jbc.M509039200.

Saito Y. Nakamura T. Ohyama Y. Suzuki T. Iida A. Shiraki-Iida T. et al.

Y. Ichi Nabeshima, M. Kurabayashi, R. Nagai, in vivo klotho gene delivery protects against endothelial dysfunction in multiple risk factor syndrome.

Biochem Biophys Res Commun. 276: 767-772https://doi.org/10.1006/bbrc.2000.3470Saito Y. Yamagishi T. Nakamura T. Ohyama Y. Aizawa H. Suga T. et al.

Klotho protein protects against endothelial dysfunction.

Biochem Biophys Res Commun. 248: 324-329https://doi.org/10.1006/bbrc.1998.8943Devaraj S. Syed B. Chien A. Jialal I.

Validation of an immunoassay for soluble klotho protein.

Am J Clin Pathol. 137: 479-485https://doi.org/10.1309/AJCPGPMAF7SFRBO4

Klotho in diabetes and diabetic nephropathy: a brief update review.

Int J Clin Exp Med. 10: 4342-4349Nie F. Wu D. Du H. Yang X. Yang M. Pang X. et al.

Serum klotho protein levels and their correlations with the progression of type 2 diabetes mellitus.

J Diabetes Complications. 31: 594-598https://doi.org/10.1016/J.JDIACOMP.2016.11.008Kunert S.K. Hartmann H. Haffner D. Leifheit-Nestler M.

Klotho and fibroblast growth factor 23 in cerebrospinal fluid in children.

J Bone Miner Metab. 35: 215-226https://doi.org/10.1007/s00774-016-0746-ySemba R.D. Moghekar A.R. Hu J. Sun K. Turner R. Ferrucci L. et al.

Klotho in the cerebrospinal fluid of adults with and without Alzheimer's disease.

Neurosci Lett. 558: 37-40https://doi.org/10.1016/j.neulet.2013.10.058Emami Aleagha M.S. Siroos B. Ahmadi M. Balood M. Palangi A. Haghighi A.N. et al.

Decreased concentration of klotho in the cerebrospinal fluid of patients with relapsing-remitting multiple sclerosis.

J Neuroimmunol. 281: 5-8https://doi.org/10.1016/j.jneuroim.2015.02.004Urakawa I. Yamazaki Y. Shimada T. Iijima K. Hasegawa H. Okawa K. et al.

Klotho converts canonical FGF receptor into a specific receptor for FGF23.

Nature. 444: 770-774https://doi.org/10.1038/nature05315

G. Chen, Y. Liu, R. Goetz, L. Fu, S. Jayaraman, M.-C. Hu, O.W. Moe, G. Liang, X. Li, M. Mohammadi, α-Klotho is a non-enzymatic molecular scaffold for FGF23 hormone signalling, Nature. 553 (2018) 461–466. doi:https://doi.org/10.1038/nature25451.

Mohammadi M. Olsen S.K. Ibrahimi O.A.

Structural basis for fibroblast growth factor receptor activation.

Cytokine Growth Factor Rev. 16: 107-137https://doi.org/10.1016/j.cytogfr.2005.01.008Yoshida T. Fujimori T. Nabeshima Y.-I.

Mediation of unusually high concentrations of 1,25-Dihydroxyvitamin D in homozygous klotho mutant mice by increased expression of renal 1α-hydroxylase gene.

Endocrinology. 143: 683-689https://doi.org/10.1210/endo.143.2.8657

Klotho, an important new factor for the activity of Ca2+ channels, connecting calcium homeostasis, ageing and uraemia.

Nephrol Dial Transplant. 21: 1770-1772https://doi.org/10.1093/ndt/gfl178Martin A. David V. Darryl Quarles L.

Regulation and function of the FGF23/klotho endocrine pathways.

Physiol Rev. 92: 131-155https://doi.org/10.1152/physrev.00002.2011

Klotho as a regulator of fibroblast growth factor signaling and phosphate/calcium metabolism.

Curr Opin Nephrol Hypertens. 15: 437-441https://doi.org/10.1097/01.mnh.0000232885.81142.83Shimada T. Kakitani M. Yamazaki Y. Hasegawa H. Takeuchi Y. Fujita T. et al.

Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism.

J Clin Invest. 113: 561-568https://doi.org/10.1172/jci19081Tang X. Wang Y. Fan Z. Ji G. Wang M. Lin J. et al.

Klotho: a tumor suppressor and modulator of the Wnt/β-catenin pathway in human hepatocellular carcinoma.

Lab Invest. 96: 197-205https://doi.org/10.1038/labinvest.2015.86

H. Liu, M.M. Fergusson, R.M. Castilho, J. Liu, L. Cao, J. Chen, D. Malide, I.I. Rovira, D. Schimel, C.J. Kuo, J.S. Gutkind, P.M. Hwang, T. Finkel, Augmented Wnt Signaling in a Mammalian Model of Accelerated Aging, Science (80-. ). 317 (2007) 803–806. doi:https://doi.org/10.1126/science.1143578.

L. Zhou, Y. Li, D. Zhou, R.J. Tan, Y. Liu, Loss of Klotho Contributes to Kidney Injury by Derepression of Wnt/β-Catenin Signaling, J. Am. Soc. Nephrol. 24 (2013).

Q. Chang, S. Hoefs, A.W. van der Kemp, C.N. Topala, R.J. Bindels, J.G. Hoenderop, The ß-Glucuronidase Klotho Hydrolyzes and Activates the TRPV5 Channel, Science (80-. ). 310 (2005).

Lee J. Tsogbadrakh B. Yang S.H. Ryu H. Kang E. Kang M. et al.

Klotho ameliorates diabetic nephropathy via LKB1-AMPK-PGC1α-mediated renal mitochondrial protection.

Biochem Biophys Res Commun. https://doi.org/10.1016/j.bbrc.2020.10.040Zeldich E. Chen C.-D. Colvin T.A. Bove-Fenderson E.A. Liang J. Tucker Zhou T.B. et al.

The neuroprotective effect of klotho is mediated via regulation of members of the redox system.

J Biol Chem. 289: 24700-24715https://doi.org/10.1074/jbc.M114.567321Gu H. Jiang W. You N. Huang X. Li Y. Peng X. et al.

Soluble klotho improves hepatic glucose and lipid homeostasis in type 2 diabetes.

Mol Ther - Methods Clin Dev. 18: 811-823https://doi.org/10.1016/j.omtm.2020.08.002

Genetic deficiency of anti-aging gene klotho exacerbates early nephropathy in STZ-induced diabetes in male mice.

Endocrinology. 154: 3855-3863https://doi.org/10.1210/en.2013-1053

A. Corcillo, N. Fountoulakis, A. Sohal, F. Farrow, S. Ayis, J. Karalliedde, Low levels of circulating anti-ageing hormone klotho predict the onset and progression of diabetic retinopathy, Diabetes Vasc Dis Res 17 (2020) 147916412097090. doi:https://doi.org/10.1177/1479164120970901.

Kim H.J. Lee J. Chae D.W. Lee K.B. Sung S.A. Yoo T.H. et al.

Serum klotho is inversely associated with metabolic syndrome in chronic kidney disease: results from the KNOW-CKD study.

BMC Nephrol. 20: 119https://doi.org/10.1186/s12882-019-1297-yJi B. Wei H. Ding Y. Liang H. Yao L. Wang H. et al.

Protective potential of klotho protein on diabetic retinopathy: evidence from clinical and in vitro studies.

J Diabetes Investig. 11: 162-169https://doi.org/10.1111/jdi.13100Lorenzi O. Veyrat-Durebex C. Wollheim C.B. Villemin P. Rohner-Jeanrenaud F. Zanchi A. et al.

Evidence against a direct role of klotho in insulin resistance.

Pflugers Arch Eur J Physiol. 459: 465-473https://doi.org/10.1007/s00424-009-0735-2van Ark J. Hammes H.-P. van Dijk M.C.R.F. Vervloet M.G. Wolffenbuttel B.H.R. van Goor H. et al.

Circulating alpha-klotho levels are not disturbed in patients with type 2 diabetes with and without macrovascular disease in the absence of nephropathy.

Cardiovasc Diabetol. 12: 116Chihara Y. Rakugi H. Ishikawa K. Ikushima M. Maekawa Y. Ohta J. et al.

Klotho protein promotes adipocyte differentiation.

Endocrinology. 147: 3835-3842https://doi.org/10.1210/en.2005-1529Xu J. Lloyd D.J. Hale C. Stanislaus S. Chen M. Sivits G. et al.

Fibroblast growth factor 21 reverses hepatic steatosis, increases energy expenditure, and improves insulin sensitivity in diet-induced obese mice.

Diabetes. 58: 250-259https://doi.org/10.2337/db08-0392

I.N. Foltz, S. Hu, C. King, X. Wu, C. Yang, W. Wang, J. Weiszmann, J. Stevens, J.S. Chen, N. Nuanmanee, J. Gupte, R. Komorowski, L. Sekirov, T. Hager, T. Arora, H. Ge, H. Baribault, F. Wang, J. Sheng, M. Karow, M. Wang, Y. Luo, W. McKeehan, Z. Wang, M.M. Veniant, Y. Li, Treating Diabetes and Obesity with an FGF21-Mimetic Antibody Activating the Klotho/FGFR1c Receptor Complex, Sci. Transl. Med. 4 (2012) 162ra153-162ra153. doi:https://doi.org/10.1126/scitranslmed.3004690.

Antonellis P.J. Droz B.A. Cosgrove R. O'Farrell L.S. Coskun T. Perfield J.W. et al.

The anti-obesity effect of FGF19 does not require UCP1-dependent thermogenesis.

Mol. Metab. 30: 131-139https://doi.org/10.1016/j.molmet.2019.09.006Samms R. Antonellis P. Bauer S. Smith D. O'Farrell L. Culver A. et al.

The anti-obesity effect of FGF19 occurs independent of the thermogenic protein UCP1 | the FASEB journal, FASEB.

Kwon M.M. O'Dwyer S.M. Baker R.K. Covey S.D. Kieffer T.J.

FGF21-mediated improvements in glucose clearance require uncoupling protein 1.

Cell Rep. 13: 1521-1527https://doi.org/10.1016/j.celrep.2015.10.021Mutsnaini L. Kim C.S. Kim J. Joe Y. Chung H.T. Choi H.S. et al.

Fibroblast growth factor 21 deficiency aggravates obesity-induced hypothalamic inflammation and impairs thermogenic response.

Inflamm Res. 68: 351-358https://doi.org/10.1007/s00011-019-01222-2Vinales K.L. Begaye B. Bogardus C. Walter M. Krakoff J. Piaggi P.

FGF21 is a hormonal mediator of the human “thrifty” metabolic phenotype.

Diabetes. 68: 318-323https://doi.org/10.2337/db18-0696

C.M. Hill, T. Laeger, M. Dehner, D.C. Albarado, B. Clarke, D. Wanders, S.J. Burke, J.J. Collier, E. Qualls-Creekmore, S.M. Solon-Biet, S.J. Simpson, H.R. Berthoud, H. Münzberg, C.D. Morrison, FGF21 Signals Protein Status to the Brain and Adaptively Regulates Food Choice and Metabolism, Cell Rep. 27 (2019) 2934–2947.e3. doi:https://doi.org/10.1016/j.celrep.2019.05.022.

Yie J. Wang W. Deng L. Tam L.-T. Stevens J. Chen M.M. et al.

Understanding the physical interactions in the FGF21/FGFR/β-klotho complex: structural requirements and implications in FGF21 signaling.

Chem Biol Drug Des. 79: 398-410https://doi.org/10.1111/j.1747-0285.2012.01325.xLee S. Choi J. Mohanty J. Sousa L.P. Tome F. Pardon E. et al.

Structures of β-klotho reveal a ‘zip code’-like mechanism for endocrine FGF signalling.

Nature. 553: 501-505https://doi.org/10.1038/nature25010

Klotho and βKlotho, in: Springer.

NY, New York: 25-40https://doi.org/10.1007/978-1-4614-0887-1_2

A. Satoh, S. iee Han, M. Araki, Y. Nakagawa, H. Ohno, Y. Mizunoe, K. Kumagai, Y. Murayama, Y. Osaki, H. Iwasaki, M. Sekiya, M. Konishi, N. Itoh, T. Matsuzaka, H. Sone, H. Shimano, CREBH Improves Diet-Induced Obesity, Insulin Resistance, and Metabolic Disturbances by FGF21-Dependent and FGF21-Independent Mechanisms, IScience. 23 (2020). doi:https://doi.org/10.1016/j.isci.2020.100930.

Fisher F.F. Kleiner S. Douris N. Fox E.C. Mepani R.J. Verdeguer F. et al.

FGF21 regulates PGC-1α and browning of white adipose tissues in adaptive thermogenesis.

Genes Dev. 26: 271-281https://doi.org/10.1101/gad.177857.111Samms R.J. Cheng C.C. Kharitonenkov A. Gimeno R.E. Adams A.C.

Overexpression of β-klotho in adipose tissue sensitizes male mice to endogenous FGF21 and provides protection from diet-induced obesity.

留言 (0)

沒有登入
gif