[1] Berti , L.,Irmler , M.,Zdichavsky , M.,Meile , T.,Böhm , A.,Stefan , N.,Fritsche , A .,Beckers , J.,Königsrainer .A., Ulrich,Häring,Staiger, .Fibroblast growth factor 21 is elevated in metabolically unhealthy obesity and affects lipid deposition, adipogenesis, and adipokine secretion of human abdominal subcutaneous adipocytes, -
[2] .Fibroblast growth factor 21 predicts the metabolic syndrome and type 2 diabetes in Caucasians,Diabetes Care 36 145 -149-2013
[3] CAdams,A. , Kharitonenkov,A., 2012.FGF21: The center of a transcriptional nexus in metabolic regulation,Current diabetes reviews 8 285 -293
[4] Cao , S. S., 2014.Endoplasmic reticulum stress and oxidative stress in cell fate decision and human disease,Antioxidants & redox signaling 21 396 -413
[5] Chartoumpekis , D. V.,Zaravinos , A.,Ziros , P. G.,Iskrenova , R. P.,Psyrogiannis , A. I.,Kyriazopoulou , V. E.,Habeos , I.G., 2012.Differential expression of microRNAs in adipose tissue after long-term high-fat diet-induced obesity in mice,PLoS One 7 -
[6] 2010.Fibroblast growth factor 21 regulates energy metabolism by activating the AMPK-SIRT1- PGC-1α pathway,Proceedings of the National Academy of Sciences 107 12553 -12558
[7] Chen,Li , L.,Yang,Li , K.,Qi,Zhu , W.,Tang , Y.,Liu , H.,Boden , G., 2008.Circulating FGF21 levels in normal subjects and in newly diagnose patients with Type 2 diabetes mellitus,Experimental and Clinical Endocrinology & Diabetes 116 65 -68
[8] Choi , S. H.,Hong , E. S.,Lim , S., 2013.Clinical implications of adipocytokines and newly emerging metabolic factors with relation to insulin resistance and cardiovascular health,Frontiers in endocrinology, 4 -
[9] Chow , W. S.,Xu , A.,Woo , Y. C.,Tso , A. W.,Cheung , S. C.,Fong , C. H.,Tse , H.F.,Chau , M.T.,Cheung , B.M.,Lam , K. S.,Serum Fibroblast Growth Factor-21 Levels,Are, .Associated With Carotid Atherosclerosis Independent of Established Cardiovascular Risk FactorsSignificance, -
[10] Arteriosclerosis, 2013., 33 2454 -2459
[11] D. , Hu,C. C. , Chen,Y. , Moller,D.E. , Kharitonenkov,A., 2008.Fibroblast growth factor 21 corrects obesity in mice,Endocrinology 149 6018 -6027
[12] 2011.,Molecular cell biology 722 -
[13] Cypess , A. M.,Lehman , S.,Williams , G.,Tal , I.,Rodman , D.,Goldfine , A. B.,Kuo , F.C.,Palmer , E.L.,Tseng , Y.H.,Doria , A.,Kolodny , D.M.,Kahn , C.R., 2009.Identification and importance of brown adipose tissue in adult humans,New England Journal of Medicine 360 1509 -1517
[14] Cyphert , H. A.,Ge , X.,Kohan , A. B.,Salati , L. M.,Zhang , Y.,Hillgartner , F. B., 2012.Activation of the farnesoid X receptor induces hepatic expression and secretion of fibroblast growth factor 21,Journal of Biological Chemistry 287 25123 -25138
[15] Díaz-Delfín , J.,Hondares , E.,Iglesias , R.,Giralt , M.,Caelles , C.,Villarroya , F., 2012.TNF-α represses β- Klotho expression and impairs FGF21 action in adipose cells: involvement of JNK1 in the FGF21 pathway,Endocrinology 153 4238 -4245
[16] Domouzoglou , E. M.,Naka , K. K.,Vlahos , A. P.,Papafaklis , M. I.,Michalis , L. K.,Tsatsoulis , A.,Maratos-Flier , E., 2015.Fibroblast growth factors in cardiovascular disease: The emerging role of FGF21,American Journal of Physiology-Heart and Circulatory Physiology 309 H1029 -H1038
[17] Dushay , J.,Chui , P. C.,Gopalakrishnan , G. S.,Varela-Rey , M.,Crawley , M.,Fisher , F. M.,Badman , M.K.,Martinez-Chantar , M.L.,Maratos-Flier , E., 2010.Increased fibroblast growth factor 21 in obesity and nonalcoholic fatty liver disease,Gastroenterology 139 456 -463
[18] A., 2012.Fibroblast growth factor-21 regulates PPARγ activity and the antidiabetic actions of thiazolidinediones,Cell 148 556 -567
[19] 2014.Myokines in insulin resistance and type 2 diabetes, 57 1087 -1099
[20] Feingold , K. R.,Grunfeld , C.,Heuer , J. G.,Gupta , A.,Cramer , M.,Zhang , T.,Shigenaga , J.K.,Patzek , S.M.,Chan , Z.W.,Moser , A.,Bina , H.,Kharitonenkov , A., 2012.FGF21 is increased by inflammatory stimuli and protects leptindeficient ob/ob mice from the toxicity of sepsis,Endocrinology 153 2689 -2700
[21] Fenzl , A.,Kiefer , F. W., 2014.Brown adipose tissue and thermogenesis,Hormone molecular biology and clinical investigation 19 25 -37
[22] 2012.FGF21 regulates PGC-539 1alpha and browning of white adipose tissues in adaptive thermogenesis,Genes & development 540 271 -281
[23] .Fibroblast growth factor 21 limits lipotoxicity by promoting hepatic fatty acid activation in mice on methionine and choline-deficient diets,Gastroenterology 147 1073 -1083
[24] 2014., -
[25] Gallego-Escuredo , J.,Gomez-Ambrosi , J.,Catalan , V.,Domingo , P.,Giralt , M.,Frühbeck , G.,Villarroya , F., 2015.Opposite alterations in FGF21 and FGF19 levels and disturbed expression of the receptor machinery for endocrine FGFs in obese patients,International journal of obesity 121 -
[26] Gälman , C.,Lundåsen , T.,Kharitonenkov , A.,Bina , H. A.,Eriksson , M.,Hafström , I.,Dahlin , M.,Amark , P.,Angelin , B.,Rudling , M., 2008.The circulating metabolic regulator FGF21 is induced by prolonged fasting and PPARα activation in man,Cell metabolism 8 169 -174
[27] Gariani , K.,Drifte , G.,Dunn-Siegrist , I.,Pugin , J.,Jornayvaz , F. R.,Increased, 2013.FGF21 plasma levels in humans with sepsis and SIRS, 2 146 -153
[28] Ge , X.,Wang , Y.,Lam , K. S.,Xu , A., 2012.Metabolic actions of FGF21: molecular mechanisms and therapeutic implications,Acta Pharmaceutica Sinica B 2 350 -357
[29] 2017.Fibroblast growth factor 21 and its novel association with oxidative stress,Redox biology 11 335 -341
[30] 2008.Acanthosis nigricans: a practical approach to evaluation and management,Dermatology online journal 14 -
[31] 2011.Thermogenic activation induces FGF21 expression and release in brown adipose tissue,Journal of Biological Chemistry 286 12983 -12990
[32] Hondares , E.,Rosell , M.,Gonzalez , F. J.,Giralt , M.,Iglesias , R.,Villarroya , F.,Hepatic, .FGF21 expression is induced at birth via PPARα in response to milk intake and contributes to thermogenic activation of neonatal brown fat, -
[33] 2010.,Cell metabolism 11 206 -212
[34] MECHANISMS IN ENDOCRINOLOGY, 2012.: Biological role, clinical significance, and therapeutic possibilities of the recently discovered metabolic hormone fibroblastic growth factor 21,European Journal of Endocrinology 167 301 -309
[35] Inagaki , T., .Research perspectives on the regulation and physiological functions of FGF21 and its association with NAFLD, -
[36] .Frontiers in endocrinology, (6): 147 (, 2015) -
[37] Itoh , N., .FGF21 as a hepatokine, adipokine, and myokine in metabolism and diseases, -
[38] Frontiers in endocrinology, (5): 107 (, -2014)
[39] Itoh , N.,Ornitz , D. M., 2004.Evolution of the Fgf and Fgfr gene families,TRENDS in Genetics 20 563 -569
[40] Izumiya , Y.,Bina , H. A.,Ouchi , N.,Akasaki , Y.,Kharitonenkov , A.,Walsh , K., 2008.FGF21 is an Aktregulated myokine,FEBS letters 582 3805 -3810
[41] Jones , L. H.,Ficca , M., 2007.Is Acanthosis Nigricans a reliable indicator for risk of type 2 diabetes?,The Journal of School Nursing 23 247 -251
[42] Kharitonenkov , A., 2009.FGFs and metabolism,Current opinion in pharmacology 9 805 -810
[43] FGF-21 as a novel metabolic regulator,The Journal of clinical investigation 115 1627 -1635 2005
[44] Kharitonenkov , A.,Wroblewski , V. J.,Koester , A.,Chen , Y.-F.,Clutinger , C. K.,Tigno , X. T.,Hansen , B.C.,Shanafelt , A.B.,Etgen , G.J., .The metabolic state of diabetic monkeys is regulated by fibroblast growth factor-21., -
[45] Endocrinology, 2007., 148 774 -781
[46] 2013.Autophagy deficiency leads to protection from obesity and insulin resistance by inducing Fgf21 as a mitokine,Nature medicine 83 -
[47] Kim , S.,Choe , S.,Lee , D. K., 2016.BMP-9 enhances fibroblast growth factor 21 expression and suppresses obesity,Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease 1237 -1246
[48] Kluczynik , C. E. N.,Mariz , L. S.,Souza , L. C. F.,Solano , G. B.,Albuquerque , F. C. d. L.,Medeiros , C. C. M., 2012.Acanthosis nigricans and insulin resistance in overweight children and adolescents, 87 531 -537
[49] Krawczyk , M.,MykałaCieśla,KołodziejJaskuła , A., 2009.Acanthosis nigricans as a para neoplastic syndrome,Polskie Archiwum Medycyny Wewnętrznej 119 180 -183
[50] Laeger , T.,Henagan , T. M.,Albarado , D. C.,Redman , L. M.,Bray , G. A.,Noland , R. C.,Münzberg , H.,Hutson , S.M.,Gettys , T.W.,Schwartz , M.W.,Morrison , C.D., 2014.FGF21 is an endocrine signal of protein restriction,The Journal of clinical investigation 3913 -
[51] Li , H.,Fang , Q.,Gao , F.,Fan , J.,Zhou , J.,Wang , X.,Pan , X.,Bao , Y.,Xiang , K.,Xu , A.,Jia , W., 2010.Fibroblast growth factor 21 levels are increased in nonalcoholic fatty liver disease patients and are correlated with hepatic triglyceride,Journal of hepatology 53 934 -940
[52] Lin , Z.,Tian , H.,Lam , K. S.,Lin , S.,Hoo , R. C.,Konishi , M.,Itoh , N.,Wang , Y.,Bornstein , S.R.,Xu , A.,Li , X., .Adiponectin mediates the metabolic effects of FGF21 on glucose homeostasis and insulin sensitivity in mice., -
[53] ,Cell metabolism 17 779 -789=2013
[54] Lin , Z.,Wu , Z.,Yin , X.,Liu , Y.,Yan , X.,Lin , S.,Xiao , J.,Wang , X.,Feng , W.,Li , X., 2010.Serum levels of FGF-21 are increased in coronary heart disease patients and are independently associated with adverse lipid profile,PLoS One 5 -
[55] .Circulating FGF21 is liver derived and enhances glucose uptake during refeeding and overfeeding,Diabetes 63 4057 -4063-2014
[56] Fenretinide mediated retinoic acid receptor signalling and inhibition of ceramide biosynthesis regulates adipogenesis, lipid accumulation, mitochondrial function and nutrient stress signalling in adipocytes and adipose tissue,Biochemical pharmacology 100 86 -97-2016
[57] McMillan , A. C.,White , M. D., 2015.Induction of thermogenesis in brown and beige adipose tissues: molecular markers, mild cold exposure and novel therapies,Current Opinion in Endocrinology, Diabetes and Obesity 22 347 -352
[58] Meek , T. H.,Morton , G. J., 2016.The role of leptin in diabetes: metabolic effects,Diabetologia 59 928 -932
[59] .Fibroblast growth factor 23 and Inflammation in CKD,Clinical Journal of the American Society of Nephrology, CJN 13281211 -2012
[60] Napolitano , M.,Megna , M.,Monfrecola , G., 2015.Insulin resistance and skin diseases,The Scientific World Journal -
[61] .Identification of a novel FGF, FGF-21, preferentially expressed in the liver1, -
[62] Biochimica et Biophysica Acta (BBA)-Gene Structure, 2000., 1492 203 -206
[63] Omar , B. A.,Andersen , B.,Hald , J.,Raun , K.,Nishimura , E.,Ahrén, 2014.and Glucagon-Like Peptide 1 Contribute to Diabetes Resistance in Glucagon Receptor-Deficient Mice,Fibroblast Growth Factor 63 101 -110
[64] Peirce , V.,Vidal-Puig , A., 2013.Regulation of glucose homoeostasis by brown adipose tissue,The lancet Diabetes & endocrinology, 1 353 -360
[65] Pengfei , Xu.,Yingjie,Wenfei , Wang.,Qingyan,Zhihang,LubnaMuhi,Qiang,Mingyao,Xianlong,Deshan , Li.,Guiping, 2015.Ren. Long-Term Administration of Fibroblast Growth Factor 21 Prevents Chemically-Induced Hepatocarcinogenesis in Mice,Dig Dis Sci 60 3032 -3043
[66] Poher , A.-L.,Altirriba , J.,Veyrat-Durebex , C.,Rohner-Jeanrenaud , F., 2015.Brown adipose tissue activity as a target for the treatment of obesity/insulin resistance,Frontiers in physiology, 6 -
[67] Oxidative stress and human health,Advances in Bioscience and Biotechnology 997 - 2012
[68] Rosen , E. D.,Spiegelman , B. M., 2006.Adipocytes as regulators of energy balance and glucose homeostasis,Nature 847 -
[69] Shenglong , Zhu.,Lei,Yunzhou,Xianlong,Tianyuan,Qingyang,LubnaMuhi,Yunye,Mo,Bing,Guiping,Deshan , Li., 2014.FGF21 treatment ameliorates alcoholic fatty liver through activation of AMPK-SIRT1 pathway,Acta Biochim Biophys Sin 46 1041 -1048
[70] Adiponectin, 2016.fatty acids in the maintenance of metabolic homeostasis through adipose tissue crosstalk,Cell metabolism 23 770 -784
[71] Stojsavljević , S.,Palčić , M. G.,Jukić , L. V.,Duvnjak , L. S.,Duvnjak , M., 2014.Adipokines and proinflammatory cytokines, the key mediators in the pathogenesis of nonalcoholic fatty liver disease,World journal of gastroenterology: WJG 18070 -
[72] Van Belle , T. L.,Gysemans , C.,Mathieu , C., 2013.Vitamin D and diabetes: the odd couple,Trends in Endocrinology & Metabolism 24 561 -568
[73] Lipids in health and disease 113 - 2014
[74] .Fibroblast growth factor-21 improves pancreatic β-cell function and survival by activation of extracellular signal-regulated kinase 1/2 and Akt signaling pathways, -
[75] Diabetes, 2006., 55 2470 -2478
[76] Whittle , A. J.,Carobbio , S.,Martins , L.,Slawik , M.,Hondares , E.,Vázquez , M. J.,D. , Csikasz,R.I. , Gallego,R. , Rodriguez-Cuenca,S. , Dale,M. , Virtue,S. , Villarroya,F. , Cannon,B. , Rahmouni,K. , López,M. , Vidal-Puig,A., 2012.BMP8B increases brown adipose tissue thermogenesis through both central and peripheral actions,Cell 149 871 -885
[77] Woo , Y.,Xu , A.,Wang , Y.,Lam , K. S., 2013.Fibroblast growth factor 21 as an emerging metabolic regulator: clinical perspectives,Clinical endocrinology 78 489 -496
[78] Xu , J.,Stanislaus , S.,Chinookoswong , N.,Lau , Y. Y.,Hager , T.,Patel , J.,Ge , H.,Weiszmann , J.,Lu , S.C.,Graham , M.,Busby , J.,Hecht , R.,Li , Y.S.,Li , Y.,Lindberg , R.,Véniant , M.M., 2009.Acute glucose-lowering and insulin-sensitizing action of FGF21 in insulin-resistant mouse modelsassociation with liver and adipose tissue effects,American Journal of PhysiologyEndocrinology and Metabolism 297 E1105 -E1114
[79] Yang , M.,Dong , J.,H. , Li,L. , Yang,G., 2011.Effects of short-term continuous subcutaneous insulin infusion on fasting plasma fibroblast growth factor-21 levels in patients with newly diagnosed type 2 diabetes mellitus,PLoS One 6 -
[80] YeXianglong,J. , Ren,Xu , Pengfei.,Wu,Yu , Dan.,LiS,MuhiRasoul,Li, 2015.Deshan. Long-lasting antidiabetic efficacy of PEGylated FGF-21 and liraglutide in treatment of type 2 diabetic mice,Endocrine 49 683 -92
[81] Yu , Y.,Li , S.,Y. , Tian,G. , Yuan,Q. , Bai,F. , Wang,W. , Zhang,Z. , Ren,G.,Y. , Li,D., 2015.Fibroblast growth factor 21 (FGF21) ameliorates collagen-induced arthritis through modulating oxidative stress and suppressing nuclear factor-kappa B pathway,International immunopharmacology 25 74 -82
[82] T. Rezaei,N., 2013.Acanthosis nigricans, abnormal facial appearance and dentition in an insulin resistance syndrome,Iranian journal of pediatrics 363 -
[83] .Fenofibrate increases cardiac autophagy via FGF21/SIRT1 and prevents fibrosis and inflammation in the hearts of Type 1 diabetic mice,Clinical Science 130 625 -641-2016
[84] Ye Xianglong, Qi, J., Ren, Guiping., Xu ,Pengfei., Wu, Yun Zhu., Yu,Dan., Li S, Wu,Qiang., Muhi Rasoul,Lubna., Li ,Deshan. Long-lasting anti-diabetic efficacy of PEGylated FGF-21 and liraglutide in treatment of type 2 diabetic mice. Endocrine. 49(3):683-92 (2015).
[85] Yu, Y., Li, S., Liu, Y., Tian, G., Yuan, Q., Bai, F., Wang, W., Zhang, Z., Ren, G., Zhang, Y., Li, D., Fibro blast growth factor 21 (FGF21) ameliorates collagen-induced arthritis through modulating oxidative stress and suppressing nuclear factor-kappa B pathway. International immunopharmacology, 25(1): 74-82 (2015).
[86] Zaridoust, A., Rabbani, A., Sayarifard, F., Thiel, C. T.,Rezaei, N. Acanthosis nigricans, abnormal facial appearance and dentition in an insulin resistance syndrome. Iranian journal of pediatrics, 23(3): 363 (2013).
[87] Zhang, J., Cheng, Y., Gu, J., Wang, S., Zhou, S., Wang, Y., Tan, Y., Feng ,W., Fu, Y., Mellen, N., Cheng, R., Ma ,J., Zhang, C., Li, Z., Cai, L. Fenofibrate increases cardiac autophagy via FGF21/SIRT1 and prevents fibrosis and inflammation in the hearts of Type 1 diabetic mice. Clinical Science, 130(8): 625-641 (2016).