Kusminski, C. M., Fernandez da Silva, Nancy, Creely, Steven J., Fisher, Ffolliott M., Harte, A. L. (Alison L.), Baker, Adam R., Kumar, Sudhesh and McTernan, P. G. (Philip G.). (2007) The in vitro effects of resistin on the innate immune signaling pathway in isolated human subcutaneous adipocytes. Journal of Clinical Endocrinology & Metabolism , Vol.92 (No.1). pp. 270-276. ISSN 0021-972x

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Abstract

Context: Obesity-associated inflammation is a contributory factor in the pathogenesis of type 2 diabetes mellitus (T2DM); the mechanisms underlying the progression to T2DM are unclear. The adipokine resistin has demonstrated pro-inflammatory properties in relation to obesity and T2DM. Objective: To characterize resistin expression in human obesity and address the role of resistin in the innate immune pathway. Furthermore, examine the influence of lipopolysaccharide, recombinant human resistin (rhResistin), insulin and rosiglitazone in human adipocytes. Finally, analyze the effect of rhResistin on the expression of components of the NF-κB pathway and insulin signaling cascade. Methods: Abdominal subcutaneous adipose tissue was obtained from patients undergoing elective liposuction surgery (n = 35, aged: 36-49 yr; BMI: 26.5 ± 5.9 kg/m2). Isolated adipocytes were cultured with rhResistin (10-50 ng/ml). The level of cytokine secretion from isolated adipocytes was examined by ELISA. The effect of rhResistin on protein expression of components of the innate immune pathway was examined by Western blot. Results: In-vitro studies demonstrated that antigenic stimuli increase resistin secretion (P < 0.001) from isolated adipocytes. Pro-inflammatory cytokine levels were increased in response to rhResistin (P < 0.001); this was attenuated by rosiglitazone (P < 0.01). When examining components of the innate immune pathway, rhResistin stimulated Toll-like receptor-2 protein expression. Similarly, mediators of the insulin signaling pathway, phosphospecific JNK1 and JNK2, were upregulated in response to rhResistin. Conclusion: Resistin may participate in more than one mechanism to influence pro-inflammatory cytokine release from human adipocytes; potentially via the integration of NF-κB and JNK signaling pathways.

Item Type:	Journal Article
Subjects:	R Medicine > RC Internal medicine
Library of Congress Subject Headings (LCSH):	Adipose tissues, Diabetes -- Research, Obesity
Journal or Publication Title:	Journal of Clinical Endocrinology & Metabolism
Publisher:	Endocrine Society
ISSN:	0021-972x
Date:	2007
Volume:	Vol.92
Number:	No.1
Page Range:	pp. 270-276
Identification Number:	10.1210/jc.2006-1151
Status:	Peer Reviewed
Access rights to Published version:	Open Access
Description:	Version accepted by publisher (post-print, after peer review, before copy-editing).
References:	1. Rajala MW, Scherer PE 2003 Minireview: The adipocyte--at the crossroads of energy homeostasis, inflammation, and atherosclerosis. Endocrinology 144:3765-73 2. Tzou P, De Gregorio E, Lemaitre B 2002 How Drosophila combats microbial infection: a model to study innate immunity and host-pathogen interactions. Current Opinion in Microbiology 5:102-110 3. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW, Jr. 2003 Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112:1796-808 4. Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H 2003 Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112:1821-30 5. Kusminski CM, McTernan PG, Kumar S 2005 Role of resistin in obesity, insulin resistance and Type II diabetes. Clin Sci (Lond) 109:243-56 6. Rangwala SM, Rich AS, Rhoades B, Shapiro JS, Obici S, Rossetti L, Lazar MA 2004 Abnormal glucose homeostasis due to chronic hyperresistinemia. Diabetes 53:1937-41 7. Silswal N, Singh AK, Aruna B, Mukhopadhyay S, Ghosh S, Ehtesham NZ 2005 Human resistin stimulates the pro-inflammatory cytokines TNF-alpha and IL-12 in macrophages by NF-kappaB-dependent pathway. Biochem Biophys Res Commun 334:1092-101 8. Bokarewa M, Nagaev I, Dahlberg L, Smith U, Tarkowski A 2005 Resistin, an adipokine with potent proinflammatory properties. J Immunol 174:5789-95 9. Savage DB, Sewter CP, Klenk ES, Segal DG, Vidal-Puig A, Considine RV, O'Rahilly S 2001 Resistin / Fizz3 expression in relation to obesity and peroxisome proliferator-activated receptor-gamma action in humans. Diabetes 50:2199-202 10. Patel L, Buckels AC, Kinghorn IJ, Murdock PR, Holbrook JD, Plumpton C, Macphee CH, Smith SA 2003 Resistin is expressed in human macrophages and directly regulated by PPAR gamma activators. Biochem Biophys Res Commun 300:472-6 11. Pagano C, Marin O, Calcagno A, Schiappelli P, Pilon C, Milan G, Bertelli M, Fanin E, Andrighetto G, Federspil G, Vettor R 2005 Increased Serum Resistin in Adults with Prader-Willi Syndrome Is Related to Obesity and Not to Insulin Resistance. J Clin Endocrinol Metab 90:4335-4340 12. Curat CA, Wegner V, Sengenes C, Miranville A, Tonus C, Busse R, Bouloumie A 2006 Macrophages in human visceral adipose tissue: increased accumulation in obesity and a source of resistin and visfatin. Diabetologia 49:744-7 13. McTernan PG, Fisher FM, Valsamakis G, Chetty R, Harte A, McTernan CL, Clark PM, Smith SA, Barnett AH, Kumar S 2003 Resistin and type 2 diabetes: regulation of resistin expression by insulin and rosiglitazone and the effects of recombinant resistin on lipid and glucose metabolism in human differentiated adipocytes. J Clin Endocrinol Metab 88:6098-106 14. McTernan PG, McTernan CL, Chetty R, Jenner K, Fisher FM, Lauer MN, Crocker J, Barnett AH, Kumar S 2002 Increased resistin gene and protein expression in human abdominal adipose tissue. J Clin Endocrinol Metab 87:2407 15. Ridker PM, Rifai N, Rose L, Buring JE, Cook NR 2002 Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med 347:1557-65 16. 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. Diabetes Care 27:2450-7 17. Reilly MP, Lehrke M, Wolfe ML, Rohatgi A, Lazar MA, Rader DJ 2005 Resistin is an inflammatory marker of atherosclerosis in humans. Circulation 111:932-9 18. Lehrke M, Reilly MP, Millington SC, Iqbal N, Rader DJ, Lazar MA 2004 An Inflammatory Cascade Leading to Hyperresistinemia in Humans. Plos Med 1:e45 19. Lin Y, Lee H, Berg AH, Lisanti MP, Shapiro L, Scherer PE 2000 The lipopolysaccharide-activated toll-like receptor (TLR)-4 induces synthesis of the closely related receptor TLR-2 in adipocytes. J Biol Chem 275:24255-63 20. Hirosumi J, Tuncman G, Chang L, Gorgun CZ, Uysal KT, Maeda K, Karin M, Hotamisligil GS 2002 A central role for JNK in obesity and insulin resistance. Nature 420:333-6 21. Steppan CM, Wang J, Whiteman EL, Birnbaum MJ, Lazar MA 2005 Activation of SOCS-3 by resistin. Mol Cell Biol 25:1569-75 22. Fu Y, Luo L, Luo N, Garvey WT 2006 Proinflammatory cytokine production and insulin sensitivity regulated by overexpression of resistin in 3T3-L1 adipocytes. Nutrition & Metabolism 3:28 23. Rae C, Graham A 2006 Human resistin promotes macrophage lipid accumulation. Diabetologia 49:1112-4 24. Baan B, van Dam H, van der Zon GC, Maassen JA, Ouwens DM 2006 The role of JNK, p38 and ERK MAP-kinases in insulin-induced Thr69 and Thr71-phosphorylation of transcription factor ATF2. Mol Endocrinol 25. Bradford MM 1976 A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248-54 26. Rajala MW, Obici S, Scherer PE, Rossetti L 2003 Adipose-derived resistin and gut-derived resistin-like molecule-beta selectively impair insulin action on glucose production. J Clin Invest 111:225-30 27. Sato N, Kobayashi K, Inoguchi T, Sonoda N, Imamura M, Sekiguchi N, Nakashima N, Nawata H 2005 Adenovirus-mediated high expression of resistin causes dyslipidemia in mice. Endocrinology 146:273-9 28. Banerjee RR, Rangwala SM, Shapiro JS, Rich AS, Rhoades B, Qi Y, Wang J, Rajala MW, Pocai A, Scherer PE, Steppan CM, Ahima RS, Obici S, Rossetti L, Lazar MA 2004 Regulation of fasted blood glucose by resistin. Science 303:1195-8 29. Graveleau C, Zaha VG, Mohajer A, Banerjee RR, Dudley-Rucker N, Steppan CM, Rajala MW, Scherer PE, Ahima RS, Lazar MA, Abel ED 2005 Mouse and Human Resistin Impair Glucose Transport in Primary Mouse Cardiomyocytes, and Oligomerization Is Required for This Biological Action. J. Biol. Chem. 280:31679-31685 30. 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 145:2206-13 31. Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM 1995 Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest 95:2409-15 32. Creely SJ Ff, Harte AL, McTernan PG, Kumar S 2006 Sub-clinical inflammation in T2DM: the role of toll like receptors in the activation of NF-κB and c-Jun kinase in 19 the innate immune pathway in human abdominal isolated adipocytes and explants. European Association for the Study of Diabetes, Copenhagen, Denmark 0121 (Abstract) 33. Li LF, Ouyang B, Choukroun G, Matyal R, Mascarenhas M, Jafari B, Bonventre JV, Force T, Quinn DA 2003 Stretch-induced IL-8 depends on c-Jun NH2-terminal and nuclear factor-kappaB-inducing kinases. Am J Physiol Lung Cell Mol Physiol 285:L464-75 34. Roeder A, Kirschning CJ, Schaller M, Weindl G, Wagner H, Korting HC, Rupec RA 2004 Induction of nuclear factor- kappa B and c-Jun/activator protein-1 via toll-like receptor 2 in macrophages by antimycotic-treated Candida albicans. J Infect Dis 190:1318-26 35. Aranda A, Pascual A 2001 Nuclear hormone receptors and gene expression. Physiol Rev 81:1269-304 36. Borst SE, Conover CF, Bagby GJ 2005 Association of resistin with visceral fat and muscle insulin resistance. Cytokine 32:39-44 37. Einstein FH, Atzmon G, Yang XM, Ma XH, Rincon M, Rudin E, Muzumdar R, Barzilai N 2005 Differential responses of visceral and subcutaneous fat depots to nutrients. Diabetes 54:672-8 38. Steppan CM, Lazar MA 2004 The current biology of resistin. J Intern Med 255:439-47
URI:	http://wrap.warwick.ac.uk/id/eprint/166

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