Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Fetuin-A: a novel link between obesity and related complications

Subjects

Abstract

Fetuin-A (FetA) is a 64-kDa glycoprotein that is secreted from both the liver and adipose tissue. Circulating FetA is elevated in obesity and related disorders including type 2 diabetes mellitus, nonalcoholic fatty liver disease and the metabolic syndrome; and a FetA-related parameter, caliciprotein particle, is highly relevant to vascular calcification in overweight/obese patients with chronic kidney disease. FetA level is also associated with impaired insulin sensitivity and glucose tolerance. Accumulating evidence suggests that elevated FetA level causes impaired glycemic control, as FetA has been implicated in impairment of insulin receptor signaling, toll-like receptor 4 activation, macrophage migration and polarization, adipocyte dysfunction, hepatocyte triacylglycerol accumulation and liver inflammation and fibrosis. Weight loss, aerobic exercise, metformin and pioglitazone have each been shown to be effective for reducing FetA level.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Ix JH, Wassel CL, Kanaya AM, Vittinghoff E, Johnson KC, Koster A et al. Fetuin-A and incident diabetes mellitus in older persons. JAMA 2008; 300: 182–188.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Stefan N, Fritsche A, Weikert C, Boeing H, Joost H-G, Häring H-U et al. Plasma fetuin-A levels and the risk of type 2 diabetes. Diabetes 2008; 57: 2762–2767.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Stefan N, Hennige AM, Staiger H, Machann J, Schick F, Kröber SM et al. α2-Heremans-Schmid glycoprotein/fetuin-A is associated with insulin resistance and fat accumulation in the liver in humans. Diabetes Care 2006; 29: 853–857.

    Article  CAS  PubMed  Google Scholar 

  4. Pedersen KO . Fetuin, a new globulin isolated from serum. Nature 1944; 154: 575–575.

    Article  CAS  Google Scholar 

  5. Olivier E, Soury E, Ruminy P, Husson A, Parmentier F, Daveau M et al. Fetuin-B, a second member of the fetuin family in mammals. Biochem J 2000; 350: 589–597.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Schultze H, Heide K, Haupt H . Charakterisierung eines niedermolekularen α 2-Mukoids aus Humanserum. Naturwissenschaften 1962; 49: 15–15.

    Article  CAS  Google Scholar 

  7. Heremans J . Les globulines seriques du systeme gamma: leur nature et leur pathologie In: Arscia. Brussels, 1960.

    Google Scholar 

  8. Bürgi W, Schmid K . Preparation and properties of Zn-α2-glycoprotein of normal human plasma. J Biol Chem 1961; 236: 1066–1074.

    Article  PubMed  Google Scholar 

  9. Brix JM, Stingl H, Höllerl F, Schernthaner GH, Kopp H-P, Schernthaner G . Elevated Fetuin-A concentrations in morbid obesity decrease after dramatic weight loss. J Clin Endocrinol Metab 2010; 95: 4877–4881.

    Article  CAS  PubMed  Google Scholar 

  10. Ix JH, Shlipak MG, Brandenburg VM, Ali S, Ketteler M, Whooley MA . Association between human fetuin-A and the metabolic syndrome data from the heart and soul study. Circulation 2006; 113: 1760–1767.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Ou H-Y, Yang Y-C, Wu H-T, Wu J-S, Lu F-H, Chang C-J . Increased fetuin-A concentrations in impaired glucose tolerance with or without nonalcoholic fatty liver disease, but not impaired fasting glucose. J Clin Endocrinol Metab 2012; 97: 4717–4723.

    Article  CAS  PubMed  Google Scholar 

  12. Hennige AM, Staiger H, Wicke C, Machicao F, Fritsche A, Häring H-U et al. Fetuin-A induces cytokine expression and suppresses adiponectin production. PLoS One 2008; 3: e1765.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Schäfer C, Heiss A, Schwarz A, Westenfeld R, Ketteler M, Floege J et al. The serum protein α2–Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification. J Clin Invest 2003; 112: 357–366.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Hamano T, Matsui I, Mikami S, Tomida K, Fujii N, Imai E et al. Fetuin-mineral complex reflects extraosseous calcification stress in CKD. J Am Soc Nephrol 2010; 21: 1998–2007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Choi KM, Han KA, Ahn HJ, Lee SY, Hwang SY, Kim BH et al. The effects of caloric restriction on Fetuin‐A and cardiovascular risk factors in rats and humans: a randomized controlled trial. Clin Endocrinol (Oxf) 2013; 79: 356–363.

    Article  CAS  Google Scholar 

  16. Malin SK, Del Rincon JP, Huang H, Kirwan JP . Exercise-Induced Lowering of Fetuin-A May Increase Hepatic Insulin Sensitivity. Med Sci Sports Exerc 2014; 46: 2085–2090.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Haukeland JW, Dahl TB, Yndestad A, Gladhaug IP, Løberg EM, Haaland T et al. Fetuin A in nonalcoholic fatty liver disease: in vivo and in vitro studies. Eur J Endocrinol 2012; 166: 503–510.

    Article  CAS  PubMed  Google Scholar 

  18. Mori K, Emoto M, Araki T, Yokoyama H, Lee E, Teramura M et al. Effects of pioglitazone on serum fetuin-A levels in patients with type 2 diabetes mellitus. Metabolism 2008; 57: 1248–1252.

    Article  CAS  PubMed  Google Scholar 

  19. Stefan N, Häring H-U . The role of hepatokines in metabolism. Nat Rev Endocrinol 2013; 9: 144–152.

    Article  CAS  PubMed  Google Scholar 

  20. Rasul S, Wagner L, Kautzky-Willer A . Fetuin-A and angiopoietins in obesity and type 2 diabetes mellitus. Endocrine 2012; 42: 496–505.

    Article  CAS  PubMed  Google Scholar 

  21. Laughlin GA, Barrett-Connor E, Cummins KM, Daniels LB, Wassel CL, Ix JH . Sex-specific association of fetuin-A with type 2 diabetes in older community-dwelling adults: the Rancho Bernardo study. Diabetes Care 2013; 36: 1994–2000.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Vörös K, Gráf L Jr, Prohászka Z, Gráf L, Szenthe P, Kaszás E et al. Serum fetuin‐A in metabolic and inflammatory pathways in patients with myocardial infarction. Eur J Clin Invest 2011; 41: 703–709.

    Article  PubMed  CAS  Google Scholar 

  23. Ix JH, Wassel CL, Chertow GM, Koster A, Johnson KC, Tylavsky FA et al. Fetuin-A and change in body composition in older persons. J Clin Endocrinol Metab 2009; 94: 4492–4498.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Klöting N, Fasshauer M, Dietrich A, Kovacs P, Schön MR, Kern M et al. Insulin-sensitive obesity. Am J Physiol Endocrinol Metab 2010; 299: E506–E515.

    Article  PubMed  CAS  Google Scholar 

  25. Lavebratt C, Wahlqvist S, Nordfors L, Hoffstedt J, Arner P . AHSG gene variant is associated with leanness among Swedish men. Hum Genet 2005; 117: 54–60.

    Article  CAS  PubMed  Google Scholar 

  26. Thakkinstian A, Chailurkit L, Warodomwichit D, Ratanachaiwong W, Yamwong S, Chanprasertyothin S et al. Causal relationship between body mass index and fetuin‐A level in the asian population: a bidirectional mendelian randomization study. Clin Endocrinol (Oxf) 2013; 81: 197–203.

    Article  CAS  Google Scholar 

  27. Sun Q, Cornelis MC, Manson JE, Hu FB . Plasma levels of fetuin-A and hepatic enzymes and risk of type 2 diabetes in women in the US. Diabetes 2013; 62: 49–55.

    Article  CAS  PubMed  Google Scholar 

  28. Ix JH, Biggs ML, Mukamal KJ, Kizer JR, Zieman SJ, Siscovick DS et al. Association of fetuin-A with incident diabetes mellitus in community-living older adults: the Cardiovascular Health Study. Circulation 2012; 125: 2316–2322.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Kalabay L, Cseh K, Pajor A, Baranyi E, Csakany GM, Melczer Z et al. Correlation of maternal serum fetuin/alpha2-HS-glycoprotein concentration with maternal insulin resistance and anthropometric parameters of neonates in normal pregnancy and gestational diabetes. Eur J Endocrinol 2002; 147: 243–248.

    Article  CAS  PubMed  Google Scholar 

  30. Færch K, Borch-Johnsen K, Holst JJ, Vaag A . Pathophysiology and aetiology of impaired fasting glycaemia and impaired glucose tolerance: does it matter for prevention and treatment of type 2 diabetes? Diabetologia 2009; 52: 1714–1723.

    Article  PubMed  CAS  Google Scholar 

  31. Stefan N, Sun Q, Fritsche A, Machann J, Schick F, Gerst F et al. Impact of the adipokine adiponectin and the hepatokine fetuin-A on the development of type 2 diabetes: Prospective Cohort-and Cross-Sectional Phenotyping Studies. PLoS One 2014; 9: e92238.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Andersen G, Burgdorf KS, Sparsø T, Borch-Johnsen K, Jørgensen T, Hansen T et al. AHSG tag single nucleotide polymorphisms associate with type 2 diabetes and dyslipidemia studies of metabolic traits in 7,683 White Danish subjects. Diabetes 2008; 57: 1427–1432.

    Article  CAS  PubMed  Google Scholar 

  33. Siddiq A, Lepretre F, Hercberg S, Froguel P, Gibson F . A synonymous coding polymorphism in the α2-Heremans-Schmid glycoprotein gene is associated with type 2 diabetes in French Caucasians. Diabetes 2005; 54: 2477–2481.

    Article  CAS  PubMed  Google Scholar 

  34. Jensen MK, Bartz TM, Djoussé L, Kizer JR, Zieman SJ, Rimm EB et al. Genetically elevated fetuin-A levels, fasting glucose levels, and risk of type 2 diabetes: the Cardiovascular Health study. Diabetes Care 2013; 36: 3121–3127.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Stefan N, Häring H-U . Circulating fetuin-A and free fatty acids interact to predict insulin resistance in humans. Nat Med 2013; 19: 394–395.

    Article  CAS  PubMed  Google Scholar 

  36. Jensen MK, Bartz TM, Mukamal KJ, Djoussé L, Kizer JR, Tracy RP et al. Fetuin-A, type 2 diabetes, and risk of cardiovascular disease in older adults: the Cardiovascular Health study. Diabetes Care 2013; 36: 1222–1228.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Laughlin GA, Cummins KM, Wassel CL, Daniels LB, Ix JH . The association of fetuin-A with cardiovascular disease mortality in older community-dwelling adults: the Rancho Bernardo study. J Am Coll Cardiol 2012; 59: 1688–1696.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Lorant DP, Grujicic M, Hoebaus C, Brix J-M, Hoellerl F, Schernthaner G et al. Fetuin-A levels are increased in patients with type 2 diabetes and peripheral arterial disease. Diabetes Care 2011; 34: 156–161.

    Article  CAS  PubMed  Google Scholar 

  39. Eraso LH, Ginwala N, Qasim AN, Mehta NN, Dlugash R, Kapoor S et al. Association of lower plasma fetuin-a levels with peripheral arterial disease in type 2 diabetes. Diabetes Care 2010; 33: 408–410.

    Article  CAS  PubMed  Google Scholar 

  40. Stefan N, Weikert C, Ix JH, Fritsche A, Häring H-U . Association of lower plasma fetuin-A levels with peripheral arterial disease in type 2 diabetes response to Eraso et al. Diabetes Care 2010; 33: e55–e55.

    Article  CAS  PubMed  Google Scholar 

  41. Xu Y, Xu M, Bi Y, Song A, Huang Y, Liu Y et al. Serum fetuin-A is correlated with metabolic syndrome in middle-aged and elderly Chinese. Atherosclerosis 2011; 216: 180–186.

    Article  CAS  PubMed  Google Scholar 

  42. Chen H-Y, Chiu Y-L, Hsu S-P, Pai M-F, Lai C-F, Peng Y-S et al. Association of serum fetuin A with truncal obesity and dyslipidemia in non-diabetic hemodialysis patients. Eur J Endocrinol 2009; 160: 777–783.

    Article  CAS  PubMed  Google Scholar 

  43. Vionnet N, Hani EH, Dupont S, Gallina S, Francke S, Dotte S et al. Genomewide search for type 2 diabetes–susceptibility genes in French Whites: evidence for a novel susceptibility locus for early-onset diabetes on chromosome 3q27-qter and independent replication of a type 2–diabetes locus on chromosome 1q21–q24. Am J Hum Genet 2000; 67: 1470–1480.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Rametta R, Ruscica M, Dongiovanni P, Macchi C, Fracanzani AL, Steffani L et al. Hepatic steatosis and PNPLA3 I148M variant are associated serum Fetuin‐A independently of insulin resistance. Eur J Clin Invest 2014; 44: 627–633.

    Article  CAS  PubMed  Google Scholar 

  45. Yilmaz Y, Yonal O, Kurt R, Ari F, Oral AY, Celikel CA et al. Serum fetuin A/α2HS-glycoprotein levels in patients with non-alcoholic fatty liver disease: relation with liver fibrosis. Ann Clin Biochem 2010; 47: 549–553.

    Article  PubMed  CAS  Google Scholar 

  46. Dogru T, Genc H, Tapan S, Aslan F, Ercin CN, Ors F et al. Plasma fetuin‐A is associated with endothelial dysfunction and subclinical atherosclerosis in subjects with nonalcoholic fatty liver disease. Clin Endocrinol (Oxf) 2013; 78: 712–717.

    Article  CAS  Google Scholar 

  47. Sato M, Kamada Y, Takeda Y, Kida S, Ohara Y, Fujii H et al. Fetuin‐A negatively correlates with liver and vascular fibrosis in nonalcoholic fatty liver disease subjects. Liver Int; e-pub ahead of print 26 February 2014; doi:10.1111/liv.12478.

    Article  PubMed  CAS  Google Scholar 

  48. Blacher J, Guerin AP, Pannier B, Marchais SJ, London GM . Arterial calcifications, arterial stiffness, and cardiovascular risk in end-stage renal disease. Hypertension 2001; 38: 938–942.

    Article  CAS  PubMed  Google Scholar 

  49. Evrard S, Delanaye P, Kamel S, Cristol J-P, Cavalier E . Vascular calcification: from pathophysiology to biomarkers. Clin Chim Acta 2014; 438C: 401–414.

    Google Scholar 

  50. Mehrotra R, Westenfeld R, Christenson P, Budoff M, Ipp E, Takasu J et al. Serum fetuin-A in nondialyzed patients with diabetic nephropathy: relationship with coronary artery calcification. Kidney Int 2005; 67: 1070–1077.

    Article  CAS  PubMed  Google Scholar 

  51. Smith ER, Ford ML, Tomlinson LA, Rajkumar C, McMahon LP, Holt SG . Phosphorylated fetuin-A-containing calciprotein particles are associated with aortic stiffness and a procalcific milieu in patients with pre-dialysis CKD. Nephrol Dial Transplant 2011; 27: 1957–1966.

    Article  PubMed  CAS  Google Scholar 

  52. Pasch A, Farese S, Gräber S, Wald J, Richtering W, Floege J et al. Nanoparticle-based test measures overall propensity for calcification in serum. J Am Soc Nephrol 2012; 23: 1744–1752.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Smith ER, Ford ML, Tomlinson LA, Bodenham E, McMahon LP, Farese S et al. Serum calcification propensity predicts all-cause mortality in predialysis CKD. J Am Soc Nephrol 2013; 25: 339–348.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Matsui I, Hamano T, Mikami S, Inoue K, Shimomura A, Nagasawa Y et al. Retention of fetuin-A in renal tubular lumen protects the kidney from nephrocalcinosis in rats. Am J Physiol Renal Physiol 2013; 304: F751–F760.

    Article  CAS  PubMed  Google Scholar 

  55. Lin X, Braymer H, Bray G, York D . Differential expression of insulin receptor tyrosine kinase inhibitor (fetuin) gene in a model of diet-induced obesity. Life Sci 1998; 63: 145–153.

    Article  CAS  PubMed  Google Scholar 

  56. Samocha-Bonet D, Tam CS, Campbell LV, Heilbronn LK . Raised circulating fetuin-A after 28-day overfeeding in healthy humans. Diabetes Care 2014; 37: e15–e16.

    Article  PubMed  Google Scholar 

  57. Dasgupta S, Bhattacharya S, Biswas A, Majumdar S, Mukhopadhyay S, Ray S . NF-kappaB mediates lipid-induced fetuin-A expression in hepatocytes that impairs adipocyte function effecting insulin resistance. Biochem J 2010; 429: 451–462.

    Article  CAS  PubMed  Google Scholar 

  58. Jung TW, Youn B-S, Choi HY, Lee SY, Hong HC, Yang SJ et al. Salsalate and adiponectin ameliorate hepatic steatosis by inhibition of the hepatokine fetuin-A. Biochem Pharmacol 2013; 86: 960–969.

    Article  CAS  PubMed  Google Scholar 

  59. Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE et al. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 2001; 86: 1930–1935.

    Article  CAS  PubMed  Google Scholar 

  60. Hussey SE, Lum H, Alvarez A, Cipriani Y, Garduño-Garcia J, Anaya L et al. A sustained increase in plasma NEFA upregulates the Toll-like receptor network in human muscle. Diabetologia 2013; 57: 582–591.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Takata H, Ikeda Y, Suehiro T, Ishibashi A, Inoue M, Kumon Y et al. High glucose induces transactivation of the alpha2-HS glycoprotein gene through the ERK1/2 signaling pathway. J Atheroscler Thromb 2009; 16: 448–456.

    Article  CAS  PubMed  Google Scholar 

  62. Ou H-Y, Wu H-T, Hung H-C, Yang Y-C, Wu J-S, Chang C-J . Endoplasmic reticulum stress induces the expression of fetuin-A to develop insulin resistance. Endocrinology 2012; 153: 2974–2984.

    Article  CAS  PubMed  Google Scholar 

  63. Chatterjee P, Seal S, Mukherjee S, Kundu R, Mukherjee S, Ray S et al. Adipocyte fetuin-a contributes to macrophage migration into adipose tissue and polarization of macrophages. J Biol Chem 2013; 288: 28324–28330.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Srinivas P, Wagner AS, Reddy LV, Deutsch D, Leon MA, Goustin AS et al. Serum alpha 2-HS-glycoprotein is an inhibitor of the human insulin receptor at the tyrosine kinase level. Mol Endocrinol 1993; 7: 1445–1455.

    CAS  PubMed  Google Scholar 

  65. Auberger P, Falquerho L, Contreres JO, Pages G, Cam GL, Rossi B et al. Characterization of a natural inhibitor of the insulin receptor tyrosine kinase: cDNA cloning, purification, and anti-mitogenic activity. Cell 1989; 58: 631–640.

    Article  CAS  PubMed  Google Scholar 

  66. Rauth G, Pöschke O, Fink E, Eulitz M, Tippmer S, Kellerer M et al. The nucleotide and partial amino acid sequences of rat fetuin. Eur J Biochem 1992; 204: 523–529.

    Article  CAS  PubMed  Google Scholar 

  67. Mathews ST, Srinivas PR, Leon MA, Grunberger G . Bovine fetuin is an inhibitor of insulin receptor tyrosine kinase. Life Sci 1997; 61: 1583–1592.

    Article  CAS  PubMed  Google Scholar 

  68. Mathews ST, Rakhade S, Zhou X, Parker GC, Coscina DV, Grunberger G . Fetuin-null mice are protected against obesity and insulin resistance associated with aging. Biochem Biophys Res Commun 2006; 350: 437–443.

    Article  CAS  PubMed  Google Scholar 

  69. Mathews ST, Singh GP, Ranalletta M, Cintron VJ, Qiang X, Goustin AS et al. Improved insulin sensitivity and resistance to weight gain in mice null for the Ahsg gene. Diabetes 2002; 51: 2450–2458.

    Article  CAS  PubMed  Google Scholar 

  70. Srinivas PR, Deutsch DD, Mathews ST, Goustin AS, Leon MA, Grunberger G . Recombinant human alpha 2-HS glycoprotein inhibits insulin-stimulated mitogenic pathway without affecting metabolic signalling in Chinese hamster ovary cells overexpressing the human insulin receptor. Cell Signal 1996; 8: 567–573.

    Article  CAS  PubMed  Google Scholar 

  71. Chen H, Srinivas PR, Cong L-N, Li Y, Grunberger G, Quon MJ . α2-Heremans schmid glycoprotein inhibits insulin-stimulated Elk-1 phosphorylation, but not glucose transport, in rat adipose cells 1. Endocrinology 1998; 139: 4147–4154.

    Article  CAS  PubMed  Google Scholar 

  72. Goustin AS, Derar N, Abou-Samra AB . Ahsg-fetuin blocks the metabolic arm of insulin action through its interaction with the 95-kD β-subunit of the insulin receptor. Cell Signal 2013; 25: 981–988.

    Article  CAS  PubMed  Google Scholar 

  73. Pal D, Dasgupta S, Kundu R, Maitra S, Das G, Mukhopadhyay S et al. Fetuin-A acts as an endogenous ligand of TLR4 to promote lipid-induced insulin resistance. Nat Med 2012; 18: 1279–1285.

    Article  CAS  PubMed  Google Scholar 

  74. Yang L, Zhang B, Song J, Miura K, Seki E . 695 Fetuin-a binding to TLR4 regulates NASH and fibrosis: the role of TRIF. Gastroenterology 2014; 146: S-922.

    Article  Google Scholar 

  75. Lumeng CN, Bodzin JL, Saltiel AR . Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest 2007; 117: 175–184.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Dahlman I, Eriksson P, Kaaman M, Jiao H, Lindgren C, Kere J et al. α2-Heremans–Schmid glycoprotein gene polymorphisms are associated with adipocyte insulin action. Diabetologia 2004; 47: 1974–1979.

    Article  CAS  PubMed  Google Scholar 

  77. Lavebratt C, Dungner E, Hoffstedt J . Polymorphism of the AHSG gene is associated with increased adipocyte β2-adrenoceptor function. J Lipid Res 2005; 46: 2278–2281.

    Article  CAS  PubMed  Google Scholar 

  78. Blüher M, Rudich A, Klöting N, Golan R, Henkin Y, Rubin E et al. Two patterns of adipokine and other biomarker dynamics in a long-term weight loss intervention. Diabetes Care 2012; 35: 342–349.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Reinehr T, Roth CL . Fetuin-A and its relation to metabolic syndrome and fatty liver disease in obese children before and after weight loss. J Clin Endocrinol Metab 2008; 93: 4479–4485.

    Article  CAS  PubMed  Google Scholar 

  80. Jüllig M, Yip S, Xu A, Smith G, Middleditch M, Booth M et al. Lower fetuin-A, retinol binding protein 4 and several metabolites after gastric bypass compared to sleeve gastrectomy in patients with type 2 diabetes. PLoS One 2014; 9: e96489.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. Schultes B, Frick J, Ernst B, Stefan N, Fritsche A . The effect of 6-weeks of aerobic exercise training on serum fetuin-A levels in non-diabetic obese women. Exp Clin Endocrinol Diabetes 2010; 118: 754–756.

    Article  CAS  PubMed  Google Scholar 

  82. Yang SJ, Hong HC, Choi HY, Yoo HJ, Cho GJ, Hwang TG et al. Effects of a three‐month combined exercise programme on fibroblast growth factor 21 and fetuin‐A levels and arterial stiffness in obese women. Clin Endocrinol (Oxf) 2011; 75: 464–469.

    Article  CAS  Google Scholar 

  83. Malin SK, Mulya A, Fealy CE, Haus JM, Pagadala MR, Scelsi AR et al. Fetuin-A is linked to improved glucose tolerance after short-term exercise training in nonalcoholic fatty liver disease. J Appl Physiol 2013; 115: 988–994.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Xu XJ, Valentine RJ, Ruderman NB . AMP-activated protein kinase (AMPK): does this master regulator of cellular energy state distinguish insulin sensitive from insulin resistant obesity? Curr Obes Rep 2014; 3: 248–255.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Le Cam A, Magnaldo I, Le Cam G, Auberger P . Secretion of a major phosphorylated glycoprotein by hepatocytes. Characterization of specific antibodies and investigations of the processing, excretion kinetics, and phosphorylation. J Biol Chem 1985; 260: 15965–15971.

    Article  CAS  PubMed  Google Scholar 

  86. Mathews S, Ren G, He X, Bowers R, Araya-Ramirez F, Littlefield L et al. Plasma fetuin-A and phosphofetuin-A (Ser312) responses to a single or short-term repeated bout of exercise in obese and normal-weight individuals (1028.2). FASEB J 2014; 28: 1028.2.

    Google Scholar 

  87. Yin J, Peng Y, Wu J, Wang Y, Yao L . Toll-like receptor 2/4 links to free fatty acid-induced inflammation and β-cell dysfunction. J Leukoc Biol 2014; 95: 47–52.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to J F Trepanowski.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Trepanowski, J., Mey, J. & Varady, K. Fetuin-A: a novel link between obesity and related complications. Int J Obes 39, 734–741 (2015). https://doi.org/10.1038/ijo.2014.203

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijo.2014.203

This article is cited by

Search

Quick links