Journal of Endocrinological Investigation

, Volume 39, Issue 6, pp 607–615 | Cite as

Resistin’s, obesity and insulin resistance: the continuing disconnect between rodents and humans




This review aimed to discuss the conflicting findings from resistin research in rodents and humans as well as recent advances in our understanding of resistin’s role in obesity and insulin resistance.


A comprehensive review and synthesis of resistin’s role in obesity and insulin resistance as well as conflicting findings from resistin research in rodents and humans.


In rodents, resistin is increased in high-fat/high-carbohydrate-fed, obese states characterized by impaired glucose uptake and insulin sensitivity. Resistin plays a causative role in the development of insulin resistance in rodents via 5′ AMP-activated protein kinase (AMPK)-dependent and AMPK-independent suppressor of cytokine signaling-3 (SOCS-3) signaling. In contrast to rodents, human resistin is primarily secreted by peripheral-blood mononuclear cells (PBMCs) as opposed to white adipocytes. Circulating resistin levels have been positively associated with central/visceral obesity (but not BMI) as well as insulin resistance, while other studies show no such association. Human resistin has a role in pro-inflammatory processes that have been conclusively associated with obesity and insulin resistance. PBMCs, as well as vascular cells, have been identified as the primary targets of resistin’s pro-inflammatory activity via nuclear factor-κB (NF-κB, p50/p65) and other signaling pathways.


Mounting evidence reveals a continuing disconnect between resistin’s role in rodents and humans due to significant differences between these two species with respect to resistin’s gene and protein structure, differential gene regulation, tissue-specific distribution, and insulin resistance induction as well as a paucity of evidence regarding the resistin receptor and downstream signaling mechanisms of action.


Adipocyte Adipocytokine Adipokine Insulin Obesity Resistin 


Compliance with ethical standards

Conflict of interest

The authors state that they have no conflict of interest to declare.

Ethical approval

This article does not contain any studies with human participants or animal performed by any of the authors.

Informed consent

For this type of study formal consent is not required.


  1. 1.
    A’t Hart B, Amor S, Jonker M (2004) Evaluating the validity of animal models for research into therapies for immune-based disorders. Drug Discov Today 9:517–524CrossRefGoogle Scholar
  2. 2.
    Abate N, Sallam HS, Rizzo M, Nikolic D, Obradovic M, Bjelogrlic P et al (2014) Resistin: an inflammatory cytokine. Role in cardiovascular diseases, diabetes and the metabolic syndrome. Curr Pharm Des 20:4961–4969PubMedCrossRefGoogle Scholar
  3. 3.
    Abdul-Ghani MA, Tripathy D, DeFronzo RA (2006) Contributions of β-cell dysfunction and insulin resistance to the pathogenesis of impaired glucose tolerance and impaired fasting glucose. Diab Care 29:1130–1139CrossRefGoogle Scholar
  4. 4.
    Al Hannan F, Culligan KG (2015) Human resistin and the RELM of Inflammation in diabesity. Diabetol Metab Syndr 7:1–11CrossRefGoogle Scholar
  5. 5.
    Amal S, Pasha HF, Rashad NM (2013) Association of resistin gene polymorphisms with insulin resistance in Egyptian obese patients. Gene 515:233–238CrossRefGoogle Scholar
  6. 6.
    Amato MC, Pizzolanti G, Torregrossa V, Misiano G, Milano S, Giordano C (2014) Visceral adiposity index (VAI) is predictive of an altered adipokine profile in patients with type 2 diabetes. PLoS One 9:e91969PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Asano H, Izawa H, Nagata K, Nakatochi M, Kobayashi M, Hirashiki A et al (2010) Plasma resistin concentration determined by common variants in the resistin gene and associated with metabolic traits in an aged Japanese population. Diabetologia 53:234–246PubMedCrossRefGoogle Scholar
  8. 8.
    Asensio C, Cettour-Rose P, Theander-Carrillo C, Rohner-Jeanrenaud F, Muzzin P (2004) Changes in glycemia by leptin administration or high-fat feeding in rodent models of obesity/type 2 diabetes suggest a link between resistin expression and control of glucose homeostasis. Endocrinology 145:2206–2213PubMedCrossRefGoogle Scholar
  9. 9.
    Azuma K, Katsukawa F, Oguchi S, Murata M, Yamazaki H, Shimada A et al (2003) Correlation between serum resistin level and adiposity in obese individuals. Obes Res 11:997–1001PubMedCrossRefGoogle Scholar
  10. 10.
    Banerjee RR, Rangwala SM, Shapiro JS, Rich AS, Rhoades B, Qi Y et al (2004) Regulation of fasted blood glucose by resistin. Science 303:1195–1198PubMedCrossRefGoogle Scholar
  11. 11.
    Barbosa-da-Silva S, Fraulob-Aquino JC, Lopes JR, Mandarim-de-Lacerda CA, Aguila MB (2012) Weight cycling enhances adipose tissue inflammatory responses in male mice. PLoS One 7:e39837PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Benomar Y, Gertler A, De Lacy P, Crépin D, Hamouda HO, Riffault L et al (2013) Central resistin overexposure induces insulin resistance through Toll-like receptor 4. Diabetes 62:102–114PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Bertolani C, Sancho-Bru P, Failli P, Bataller R, Aleffi S, DeFranco R et al (2006) Resistin as an intrahepatic cytokine: overexpression during chronic injury and induction of proinflammatory actions in hepatic stellate cells. Am J Pathol 169:2042–2053PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Bielohuby M, Sisley S, Sandoval D, Herbach N, Zengin A, Fischereder M et al (2013) Impaired glucose tolerance in rats fed low-carbohydrate, high-fat diets. Am J Physiol Endocrinol Metab 305:E1059–E1070PubMedCrossRefGoogle Scholar
  15. 15.
    Brunetti L, Orlando G, Recinella L, Michelotto B, Ferrante C, Vacca M (2004) Resistin, but not adiponectin, inhibits dopamine and norepinephrine release in the hypothalamus. Eur J Pharmacol 493:41–44PubMedCrossRefGoogle Scholar
  16. 16.
    Castañeda T, Nogueiras R, Müller T, Krishna R, Grant E, Jones A et al (2011) Decreased glucose tolerance and plasma adiponectin: resistin ratio in a mouse model of post-traumatic stress disorder. Diabetologia 54:900–909PubMedCrossRefGoogle Scholar
  17. 17.
    Chen Y-H, Lee M-J, Chang H-H, Hung P-F, Kao Y-H (2006) 17β-Estradiol stimulates resistin gene expression in 3T3-L1 adipocytes via the estrogen receptor, extracellularly regulated kinase, and CCAAT/enhancer binding protein-α pathways. Endocrinology 147:4496–4504PubMedCrossRefGoogle Scholar
  18. 18.
    Cherneva RV, Georgiev OB, Petrova DS, Mondeshki TL, Ruseva SR, Cakova AD et al. (2013) Resistin-the link between adipose tissue dysfunction and insulin resistance in patients with obstructive sleep apnea. J Diabetes Metab Disord 12Google Scholar
  19. 19.
    Cho YM, Youn B-S, Chung SS, Kim KW, Lee H, Yu K-Y et al (2004) Common genetic polymorphisms in the promoter of resistin gene are major determinants of plasma resistin concentrations in humans. Diabetologia 47:559–565PubMedCrossRefGoogle Scholar
  20. 20.
    Daquinag AC, Zhang Y, Amaya-Manzanares F, Simmons PJ, Kolonin MG (2011) An isoform of decorin is a resistin receptor on the surface of adipose progenitor cells. Cell Stem Cell 9:74–86PubMedCrossRefGoogle Scholar
  21. 21.
    De Luis D, Terroba M, Cuellar L, Conde R, Primo D, Aller R et al (2011) Resistin levels in morbid obese patients following the biliopancreatic diversion surgery. Horm Metab Res 43:205–208PubMedCrossRefGoogle Scholar
  22. 22.
    Felipe F, Bonet ML, Ribot J, Palou A (2004) Modulation of resistin expression by retinoic acid and vitamin A status. Diabetes 53:882–889PubMedCrossRefGoogle Scholar
  23. 23.
    Friese MA, Montalban X, Willcox N, Bell JI, Martin R, Fugger L (2006) The value of animal models for drug development in multiple sclerosis. Brain 129:1940–1952PubMedCrossRefGoogle Scholar
  24. 24.
    Gan A-M, Butoi ED, Manea A, Simion V, Stan D, Parvulescu M-M et al (2013) Inflammatory effects of resistin on human smooth muscle cells: up-regulation of fractalkine and its receptor, CX3CR1 expression by TLR4 and Gi-protein pathways. Cell Tissue Res 351:161–174PubMedCrossRefGoogle Scholar
  25. 25.
    Gerber M, Boettner A, Seidel B, Lammert A, Bar J, Schuster E et al (2005) Serum resistin levels of obese and lean children and adolescents: biochemical analysis and clinical relevance. J Clin Endocrinol Metab 90:4503–4509PubMedCrossRefGoogle Scholar
  26. 26.
    Ghosh S, Singh AK, Aruna B, Mukhopadhyay S, Ehtesham NZ (2003) The genomic organization of mouse resistin reveals major differences from the human resistin: functional implications. Gene 305:27–34PubMedCrossRefGoogle Scholar
  27. 27.
    Graveleau C, Zaha VG, Mohajer A, Banerjee RR, Dudley-Rucker N, Steppan CM et al (2005) Mouse and human resistins impair glucose transport in primary mouse cardiomyocytes, and oligomerization is required for this biological action. J Biol Chem 280:31679–31685PubMedCrossRefGoogle Scholar
  28. 28.
    Haugen F, Jørgensen A, Drevon CA, Trayhurn P (2001) Inhibition by insulin of resistin gene expression in 3T3-L1 adipocytes. FEBS Lett 507:105–108PubMedCrossRefGoogle Scholar
  29. 29.
    Heilbronn L, Rood J, Janderova L, Albu J, Kelley D, Ravussin E et al (2004) Relationship between serum resistin concentrations and insulin resistance in non-obese, obese, and obese diabetic subjects. J Clin Endocrinol Metab 89:1844–1848PubMedCrossRefGoogle Scholar
  30. 30.
    Higashida K, Fujimoto E, Higuchi M, Terada S (2013) Effects of alternate-day fasting on high-fat diet-induced insulin resistance in rat skeletal muscle. Life Sci 93:208–213PubMedCrossRefGoogle Scholar
  31. 31.
    Hivert M-F, Sullivan LM, Fox CS, Nathan DM, D’Agostino RB Sr, Wilson PW et al (2008) Associations of adiponectin, resistin, and tumor necrosis factor-α with insulin resistance. J Clin Endocrinol Metab 93:3165–3172PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Hsu WY, Chao YW, Tsai YL, Lien CC, Chang CF, Deng MC et al (2011) Resistin induces monocyte–endothelial cell adhesion by increasing ICAM-1 and VCAM-1 expression in endothelial cells via p38MAPK-dependent pathway. J Cell Physiol 226:2181–2188PubMedCrossRefGoogle Scholar
  33. 33.
    Ikeda Y, Tsuchiya H, Hama S, Kajimoto K, Kogure K (2013) Resistin affects lipid metabolism during adipocyte maturation of 3T3-L1 cells. FEBS J 280:5884–5895PubMedCrossRefGoogle Scholar
  34. 34.
    Ikeda Y, Tsuchiya H, Hama S, Kajimoto K, Kogure K (2014) Resistin regulates the expression of plasminogen activator inhibitor-1 in 3T3-L1 adipocytes. Biochem Biophys Res Commun 448:129–133PubMedCrossRefGoogle Scholar
  35. 35.
    Jain SH, Massaro JM, Hoffmann U, Rosito GA, Vasan RS, Raji A et al (2009) Cross-sectional associations bet ween abdominal and thoracic adipose tissue compartments and adiponectin and resistin in the Framingham heart study. Diab Care 32:903–908CrossRefGoogle Scholar
  36. 36.
    Johnson AM, Olefsky JM (2013) The origins and drivers of insulin resistance. Cell 152:673–684PubMedCrossRefGoogle Scholar
  37. 37.
    Juan C-C, Au L-C, Fang VS, Kang S-F, Ko Y-H, Kuo S-F et al (2001) Suppressed gene expression of adipocyte resistin in an insulin-resistant rat model probably by elevated free fatty acids. Biochem Biophys Res Commun 289:1328–1333PubMedCrossRefGoogle Scholar
  38. 38.
    Kahn BB, Flier JS (2000) Obesity and insulin resistance. J Clin Invest 106:473PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Kalueff A, Wheaton M, Murphy D (2007) What’s wrong with my mouse model?: advances and strategies in animal modeling of anxiety and depression. Behav Brain Res 179:1–18PubMedCrossRefGoogle Scholar
  40. 40.
    Kamigaki M, Sakaue S, Tsujino I, Ohira H, Ikeda D, Itoh N et al (2006) Oxidative stress provokes atherogenic changes in adipokine gene expression in 3T3-L1 adipocytes. Biochem Biophys Res Commun 339:624–632PubMedCrossRefGoogle Scholar
  41. 41.
    Kaser S, Kaser A, Sandhofer A, Ebenbichler C, Tilg H, Patsch J (2003) Resistin messenger-RNA expression is increased by proinflammatory cytokines in vitro. Biochem Biophys Res Commun 309:286–290PubMedCrossRefGoogle Scholar
  42. 42.
    Kim K-H, Lee K, Moon YS, Sul HS (2001) A cysteine-rich adipose tissue-specific secretory factor inhibits adipocyte differentiation. J Biol Chem 276:11252–11256PubMedCrossRefGoogle Scholar
  43. 43.
    Kim K-H, Zhao L, Moon Y, Kang C, Sul HS (2004) Dominant inhibitory adipocyte-specific secretory factor (ADSF)/resistin enhances adipogenesis and improves insulin sensitivity. Proc Natl Acad Sci USA 101:6780–6785PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Kusminski CM, Mcternan PG, Kumar S (2005) Role of resistin in obesity, insulin resistance and Type II diabetes. Clin Sci 109:243–256PubMedCrossRefGoogle Scholar
  45. 45.
    Kwon H, Pessin JE (2013) Adipokines mediate inflammation and insulin resistance Front Endocrinol 4Google Scholar
  46. 46.
    Lazar M (2007) Resistin-and obesity-associated metabolic diseases. Horm Metab 39:710–716CrossRefGoogle Scholar
  47. 47.
    Le Lay S, Boucher J, Rey A, Castan-Laurell I, Krief S, Ferré P et al (2001) Decreased resistin expression in mice with different sensitivities to a high-fat diet. Biochem Biophys Res Commun 289:564–567PubMedCrossRefGoogle Scholar
  48. 48.
    Lee JH, Bullen JW, Stoyneva VL, Mantzoros CS (2005) Circulating resistin in lean, obese, and insulin-resistant mouse models: lack of association with insulinemia and glycemia. Am J Physiol Endocrinol Metab 288:E625–E632PubMedCrossRefGoogle Scholar
  49. 49.
    Lee JH, Chan JL, Yiannakouris N, Kontogianni M, Estrada E, Seip R et al (2003) Circulating resistin levels are not associated with obesity or insulin resistance in humans and are not regulated by fasting or leptin administration: cross-sectional and interventional studies in normal, insulin-resistant, and diabetic subjects. J Clin Endocrinol Metab 88:4848–4856PubMedCrossRefGoogle Scholar
  50. 50.
    Lee M-J, Lin H, Liu C-W, Wu M-H, Liao W-J, Chang H-H et al (2008) Octylphenol stimulates resistin gene expression in 3T3-L1 adipocytes via the estrogen receptor and extracellular signal-regulated kinase pathways. Am J Physiol Cell Physiol 294:C1542–C1551PubMedCrossRefGoogle Scholar
  51. 51.
    Lehrke M, Reilly MP, Millington SC, Iqbal N, Rader DJ, Lazar MA (2004) An inflammatory cascade leading to hyperresistinemia in humans. PLoS Med 1:e45PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Li Y, Ding L, Hassan W, Abdelkader D, Shang J (2013) Adipokines and hepatic insulin resistance. J Diab Res 2013Google Scholar
  53. 53.
    Liu C-W, Yang S-Y, Lin C-K, Liu H-S, Ho L-T, Wu L-Y et al (2014) The forkhead transcription factor FOXO1 stimulates the expression of the adipocyte resistin gene. Gen Comp Endocrinol 196:41–51PubMedCrossRefGoogle Scholar
  54. 54.
    Lobo TF, Torloni MR, Gueuvoghlanian-Silva BY, Mattar R, Daher S (2013) Resistin concentration and gestational diabetes: a systematic review of the literature. J Reprod Immunol 97:120–127PubMedCrossRefGoogle Scholar
  55. 55.
    Luo Z, Zhang Y, Li F, He J, Ding H, Yan L et al (2009) Resistin induces insulin resistance by both AMPK-dependent and AMPK-independent mechanisms in HepG2 cells. Endocrine 36:60–69PubMedCrossRefGoogle Scholar
  56. 56.
    Manduteanu I, Pirvulescu M, Gan AM, Stan D, Simion V, Dragomir E et al (2010) Similar effects of resistin and high glucose on P-selectin and fractalkine expression and monocyte adhesion in human endothelial cells. Biochem Biophys Res Commun 391:1443–1448PubMedCrossRefGoogle Scholar
  57. 57.
    Mantovani J, Roy R (2011) Re-evaluating the general (ized) roles of AMPK in cellular metabolism. FEBS Lett 585:967–972PubMedCrossRefGoogle Scholar
  58. 58.
    Masuzaki H, Paterson J, Shinyama H, Morton NM, Mullins JJ, Seckl JR et al (2001) A transgenic model of visceral obesity and the metabolic syndrome. Science 294:2166–2170PubMedCrossRefGoogle Scholar
  59. 59.
    McTernan CL, McTernan PG, Harte AL, Levick P, Barnett A, Kumar S (2002) Resistin, central obesity, and type 2 diabetes. Lancet 359:46–47PubMedCrossRefGoogle Scholar
  60. 60.
    Menzaghi C, Coco A, Salvemini L, Thompson R, De Cosmo S, Doria A et al (2006) Heritability of serum resistin and its genetic correlation with insulin resistance-related features in nondiabetic Caucasians. J Clin Endocrinol Metab 91:2792–2795PubMedCrossRefGoogle Scholar
  61. 61.
    Milan G, Granzotto M, Scarda A, Calcagno A, Pagano C, Federspil G et al (2002) Resistin and adiponectin expression in visceral fat of obese rats: effect of weight loss. Obes Res 10:1095–1103PubMedCrossRefGoogle Scholar
  62. 62.
    Minn AH, Patterson NB, Pack S, Hoffmann SC, Gavrilova O, Vinson C et al (2003) Resistin is expressed in pancreatic islets. Biochem Biophys Res Commun 310:641–645PubMedCrossRefGoogle Scholar
  63. 63.
    Monzillo LU, Hamdy O, Horton ES, Ledbury S, Mullooly C, Jarema C et al (2003) Effect of lifestyle modification on adipokine levels in obese subjects with insulin resistance. Obes Res 11:1048–1054PubMedCrossRefGoogle Scholar
  64. 64.
    Morash BA, Willkinson D, Ur E, Wilkinson M (2002) Resistin expression and regulation in mouse pituitary. FEBS Lett 526:26–30PubMedCrossRefGoogle Scholar
  65. 65.
    Moschen AR, Molnar C, Wolf AM, Weiss H, Graziadei I, Kaser S et al (2009) Effects of weight loss induced by bariatric surgery on hepatic adipocytokine expression. J Hepatol 51:765–777PubMedCrossRefGoogle Scholar
  66. 66.
    Muse ED, Lam TK, Scherer PE, Rossetti L (2007) Hypothalamic resistin induces hepatic insulin resistance. J Clin Invest 117:1670PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Muse ED, Obici S, Bhanot S, Monia BP, McKay RA, Rajala MW et al (2004) Role of resistin in diet-induced hepatic insulin resistance. J Clin Invest 114:232PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Nagaev I, Smith U (2001) Insulin resistance and type 2 diabetes are not related to resistin expression in human fat cells or skeletal muscle. Biochem Biophys Res Commun 285:561–564PubMedCrossRefGoogle Scholar
  69. 69.
    Nieva-Vazquez A, Pérez-Fuentes R, Torres-Rasgado E, López-López JG, Romero JR (2014) Serum resistin levels are associated with adiposity and insulin sensitivity in obese hispanic subjects. Metab Syndr Relat Disord 12:143–148PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Niles LP, Lobb DK, Kang NH, Armstrong KJ (2012) Resistin expression in human granulosa cells. Endocrine 42:742–745PubMedCrossRefGoogle Scholar
  71. 71.
    Nogueiras R, Gualillo O, Caminos JE, Garcı́ T, Casanueva FF, Diéguez C (2003) Resistin is expressed in different rat tissues and is regulated in a tissue-and gender-specific manner. FEBS Lett 548:21–27PubMedCrossRefGoogle Scholar
  72. 72.
    Oliveira MC, Menezes-Garcia Z, Henriques MC, Soriani FM, Pinho V, Faria A et al (2013) Acute and sustained inflammation and metabolic dysfunction induced by high refined carbohydrate-containing diet in mice. Obesity 21:E396–E406PubMedGoogle Scholar
  73. 73.
    Oliver P, Ribot J, Rodriguez A, Sanchez J, Pico C, Palou A (2006) Resistin as a putative modulator of insulin action in the daily feeding/fasting rhythm. Pflügers Archiv 452:260–267PubMedCrossRefGoogle Scholar
  74. 74.
    Onuma H, Tabara Y, Kawamura R, Ohashi J, Nishida W, Takata Y et al (2013) Plasma resistin is associated with single nucleotide polymorphisms of a possible resistin receptor, the decorin gene, in the general Japanese population. Diabetes 62:649–652PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Ort T, Arjona AA, MacDougall JR, Nelson PJ, Rothenberg ME, Wu F et al (2005) Recombinant human FIZZ3/resistin stimulates lipolysis in cultured human adipocytes, mouse adipose explants, and normal mice. Endocrinology 146:2200–2209PubMedCrossRefGoogle Scholar
  76. 76.
    Osawa H, Onuma H, Ochi M, Murakami A, Yamauchi J, Takasuka T et al (2005) Resistin SNP-420 determines its monocyte mRNA and serum levels inducing type 2 diabetes. Biochem Biophys Res Commun 335:596–602PubMedCrossRefGoogle Scholar
  77. 77.
    Osawa H, Tabara Y, Kawamoto R, Ohashi J, Ochi M, Onuma H et al (2007) Plasma resistin, associated with single nucleotide polymorphism −420, is correlated with insulin resistance, lower HDL cholesterol, and high-sensitivity C-reactive protein in the Japanese general population. Diab Care 30:1501–1506CrossRefGoogle Scholar
  78. 78.
    Owecki M, Miczke A, Nikisch E, Pupek-Musialik D, Sowiński J (2011) Serum resistin concentrations are higher in human obesity but independent from insulin resistance. Exp Clin Endocrinol Diab Off J Ger Soc Endocrinol Ger Diab Assoc 119:117–121CrossRefGoogle Scholar
  79. 79.
    Pajvani UB, Hawkins M, Combs TP, Rajala MW, Doebber T, Berger JP et al (2004) Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedione-mediated improvement in insulin sensitivity. J Biol Chem 279:12152–12162PubMedCrossRefGoogle Scholar
  80. 80.
    Palanivel R, Maida A, Liu Y, Sweeney G (2006) Regulation of insulin signalling, glucose uptake and metabolism in rat skeletal muscle cells upon prolonged exposure to resistin. Diabetologia 49:183–190PubMedCrossRefGoogle Scholar
  81. 81.
    Park HK, Ahima RS (2013) Resistin in rodents and humans. Diab Metab J 37:404–414CrossRefGoogle Scholar
  82. 82.
    Patel L, Buckels AC, Kinghorn IJ, Murdock PR, Holbrook JD, Plumpton C et al (2003) Resistin is expressed in human macrophages and directly regulated by PPARγ activators. Biochem Biophys Res Commun 300:472–476PubMedCrossRefGoogle Scholar
  83. 83.
    Qasim AN, Metkus TS, Tadesse M, Lehrke M, Restine S, Wolfe ML et al (2009) Resistin gene variation is associated with systemic inflammation but not plasma adipokine levels, metabolic syndrome or coronary atherosclerosis in nondiabetic Caucasians. Clin Endocrinol 70:698–705CrossRefGoogle Scholar
  84. 84.
    Qatanani M, Szwergold NR, Greaves DR, Ahima RS, Lazar MA (2009) Macrophage-derived human resistin exacerbates adipose tissue inflammation and insulin resistance in mice. J Clin Investig 119:531PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Qiu W, Chen N, Zhang Q, Zhuo L, Wang X, Wang D et al (2014) Resistin increases platelet P-selectin levels via p38 MAPK signal pathway. Diab Vasc Dis Res 11:121–124PubMedCrossRefGoogle Scholar
  86. 86.
    Rajala MW, Obici S, Scherer PE, Rossetti L (2003) Adipose-derived resistin and gut-derived resistin-like molecule–β selectively impair insulin action on glucose production. J Clin Invest 111:225PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Reilly MP, Lehrke M, Wolfe ML, Rohatgi A, Lazar MA, Rader DJ (2005) Resistin is an inflammatory marker of atherosclerosis in humans. Circulation 111:932–939PubMedCrossRefGoogle Scholar
  88. 88.
    Romacho T, Elsen M, Röhrborn D, Eckel J (2014) Adipose tissue and its role in organ crosstalk. Acta Physiol 210:733–753CrossRefGoogle Scholar
  89. 89.
    Sanchez-Solana B, Laborda J, Baladron V (2011) Mouse resistin modulates adipogenesis and glucose uptake in 3T3-L1 preadipocytes through the ROR1 receptor. Mol Endocrinol 26:110–127PubMedCrossRefGoogle Scholar
  90. 90.
    Satoh H, Nguyen MA, Miles PD, Imamura T, Usui I, Olefsky JM (2004) Adenovirus-mediated chronic “hyper-resistinemia” leads to in vivo insulin resistance in normal rats. J Clin Invest 114:224PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Savage DB, Sewter CP, Klenk ES, Segal DG, Vidal-Puig A, Considine RV et al (2001) Resistin/Fizz3 expression in relation to obesity and peroxisome proliferator–activated receptor-γ action in humans. Diabetes 50:2199–2202PubMedCrossRefGoogle Scholar
  92. 92.
    Schaalan M, El-Abhar HS, Barakat M, El-Denshary ES (2009) Westernized-like-diet-fed rats: effect on glucose homeostasis, lipid profile, and adipocyte hormones and their modulation by rosiglitazone and glimepiride. J Diab Complicat 23:199–208CrossRefGoogle Scholar
  93. 93.
    Schwartz DR, Lazar MA (2011) Human resistin: found in translation from mouse to man. Trends Endocrinol Metab 22:259–265PubMedPubMedCentralGoogle Scholar
  94. 94.
    Seo JB, Noh MJ, Yoo EJ, Park SY, Park J, Lee IK et al (2003) Functional characterization of the human resistin promoter with adipocyte determination-and differentiation-dependent factor 1/sterol regulatory element binding protein 1c and CCAAT enhancer binding protein-α. Mol Endocrinol 17:1522–1533PubMedCrossRefGoogle Scholar
  95. 95.
    Sheng CH, Du ZW, Song Y, Wu XD, Zhang YC, Wu M, et al. (2013) Human resistin inhibits myogenic differentiation and induces insulin resistance in myocytes. BioMed Res Int 2013Google Scholar
  96. 96.
    Shetty GK, Economides PA, Horton ES, Mantzoros CS, Veves A (2004) Circulating adiponectin and resistin levels in relation to metabolic factors, inflammatory markers, and vascular reactivity in diabetic patients and subjects at risk for diabetes. Diab Care 27:2450–2457CrossRefGoogle Scholar
  97. 97.
    Shulman GI, Rothman DL, Jue T, Stein P, DeFronzo RA, Shulman RG (1990) Quantitation of muscle glycogen synthesis in normal subjects and subjects with non-insulin-dependent diabetes by 13C nuclear magnetic resonance spectroscopy. N Engl J Med 322:223–228PubMedCrossRefGoogle Scholar
  98. 98.
    Silswal N, Singh AK, Aruna B, Mukhopadhyay S, Ghosh S, Ehtesham NZ (2005) Human resistin stimulates the pro-inflammatory cytokines TNF-α and IL-12 in macrophages by NF-κB-dependent pathway. Biochem Biophys Res Commun 334:1092–1101PubMedCrossRefGoogle Scholar
  99. 99.
    Singhal NS, Lazar MA, Ahima RS (2007) Central resistin induces hepatic insulin resistance via neuropeptide Y. J Neurosci 27:12924–12932PubMedCrossRefGoogle Scholar
  100. 100.
    Song H, Shojima N, Sakoda H, Ogihara T, Fujishiro M, Katagiri H et al (2002) Resistin is regulated by C/EBPs, PPARs, and signal-transducing molecules. Biochem Biophys Res Commun 299:291–298PubMedCrossRefGoogle Scholar
  101. 101.
    Song R, Wang X, Mao Y, Li H, Li Z, Xu W et al (2013) Resistin disrupts glycogen synthesis under high insulin and high glucose levels by down-regulating the hepatic levels of GSK3β. Gene 529:50–56PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM et al (2001) The hormone resistin links obesity to diabetes. Nature 409:307–312PubMedCrossRefGoogle Scholar
  103. 103.
    Talmadge JE, Singh RK, Fidler IJ, Raz A (2007) Murine models to evaluate novel and conventional therapeutic strategies for cancer. Am J Pathol 170:793–804PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Tang Y-C, Liu C-W, Chang H-H, Juan C-C, Kuo Y-C, Kao C-C et al (2014) Endothelin-1 stimulates resistin gene expression. Endocrinology 155:854–864PubMedCrossRefGoogle Scholar
  105. 105.
    Tarkowski A, Bjersing J, Shestakov A, Bokarewa MI (2010) Resistin competes with lipopolysaccharide for binding to toll-like receptor 4. J Cell Mol Med 14:1419–1431PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Tomaru T, Steger DJ, Lefterova MI, Schupp M, Lazar MA (2009) Adipocyte-specific expression of murine resistin is mediated by synergism between peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding proteins. J Biol Chem 284:6116–6125PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Tontonoz P, Spiegelman BM (2008) Fat and beyond: the diverse biology of PPARγ. Annu Rev Biochem 77:289–312PubMedCrossRefGoogle Scholar
  108. 108.
    Tovar S, Nogueiras R, Tung LY, Castañeda TR, Vázquez MJ, Morris A et al (2005) Central administration of resistin promotes short-term satiety in rats. Eur J Endocrinol 153:R1–R5PubMedCrossRefGoogle Scholar
  109. 109.
    Ukkola O, Kunnari A, Kesäniemi YA (2008) Genetic variants at the resistin locus are associated with the plasma resistin concentration and cardiovascular risk factors. Regul Pept 149:56–59PubMedCrossRefGoogle Scholar
  110. 110.
    Vazquez MJ, González CR, Varela L, Lage R, Tovar S, Sangiao-Alvarellos S et al (2008) Central resistin regulates hypothalamic and peripheral lipid metabolism in a nutritional-dependent fashion. Endocrinology 149:4534–4543PubMedCrossRefGoogle Scholar
  111. 111.
    Way JM, Görgün CZ, Tong Q, Uysal KT, Brown KK, Harrington WW et al (2001) Adipose tissue resistin expression is severely suppressed in obesity and stimulated by peroxisome proliferator-activated receptor γ agonists. J Biol Chem 276:25651–25653PubMedCrossRefGoogle Scholar
  112. 112.
    Wolfe BE, Jimerson DC, Orlova C, Mantzoros CS (2004) Effect of dieting on plasma leptin, soluble leptin receptor, adiponectin and resistin levels in healthy volunteers. Clin Endocrinol 61:332–338CrossRefGoogle Scholar
  113. 113.
    Xu JY, Sham PC, Xu A, Tso AW, Wat N, Cheng KY et al (2007) Resistin gene polymorphisms and progression of glycaemia in southern Chinese: a 5-year prospective study. Clin Endocrinol 66:211–217CrossRefGoogle Scholar
  114. 114.
    Yang R-Z, Huang Q, Xu A, McLenithan JC, Eison JA, Shuldiner AR et al (2003) Comparative studies of resistin expression and phylogenomics in human and mouse. Biochem Biophys Res Commun 310:927–935PubMedCrossRefGoogle Scholar
  115. 115.
    Yannakoulia M, Yiannakouris N, Blüher S, Matalas A-L, Klimis-Zacas D, Mantzoros CS (2003) Body fat mass and macronutrient intake in relation to circulating soluble leptin receptor, free leptin index, adiponectin, and resistin concentrations in healthy humans. J Clin Endocrinol Metab 88:1730–1736PubMedCrossRefGoogle Scholar
  116. 116.
    Youn B-S, Yu K-Y, Park HJ, Lee NS, Min SS, Youn MY et al (2004) Plasma resistin concentrations measured by enzyme-linked immunosorbent assay using a newly developed monoclonal antibody are elevated in individuals with type 2 diabetes mellitus. J Clin Endocrinol Metab 89:150–156PubMedCrossRefGoogle Scholar
  117. 117.
    Zhang J, Qin Y, Zheng X, Qiu J, Gong L, Mao H et al (2002) The relationship between human serum resistin level and body fat content, plasma glucose as well as blood pressure. Zhonghua Yi Xue Za Zhi 82:1609–1612PubMedGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2015

Authors and Affiliations

  1. 1.Department of Radiology, College of Basic MedicineChongqing Medical UniversityChongqingChina
  2. 2.Department of Internal MedicineHechuan Hospital of First Affiliated Hospital of Chongqing Medical UniversityChongqingChina
  3. 3.Department of Internal Medicinethe First Affiliated Hospital of Chongqing Medical UniversityChongqingChina

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