Abstract
Objective:
Tartrate-resistant acid phosphatase (TRAP) expressed by adipose tissue macrophages (ATMs) induces mice obesity and human adipocyte differentiation in vitro. This study aimed to investigate whether TRAP was secreted differently from human obese versus lean adipose tissues and to identify the cellular source of adipose tissue TRAP.
Design:
Subcutaneous adipose tissues obtained from healthy subjects. Enzyme-linked immunosorbent assays (ELISAs) for total (5a+5b) and cleaved TRAP (5b) were used. TRAP secretion was determined in adipose tissue biopsies, and mRNA expression was studied in cell types isolated from the same.
Subjects:
Results of 24 lean and 24 obese women (in vitro) and 8 subjects (in vivo) were compared. The main outcome measurements were TRAP expression and secretion in vitro and in vivo.
Results:
In-house total TRAP ELISA showed high sensitivity and a coefficient of variance of 11%. Adipose secretion of total TRAP was linear in vitro with time and was evident in vivo. Total TRAP secretion in vitro was similar in lean and obese women expressed per unit weight of the adipose tissue but correlated positively with the number/size of adipocytes (P⩽0.01) and with adipose secretion of tumor necrosis factor-α and interleukin-6 (P<0.01). TRAP 5b was not secreted from the adipose tissue. ATMs displayed highest cellular expression of TRAP mRNA in adipose tissue cells derived from lean or obese women.
Conclusions:
TRAP is a novel human adipokine produced by macrophages and secreted from the subcutaneous adipose tissue in vivo and in vitro. Secretion is linked to the size and number of adipocytes, as well as to concomitant secretion of inflammatory mediators, suggesting that TRAP is involved in fat accumulation and adipose inflammation.
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References
Janckila AJ, Yam LT . Biology and clinical significance of tartrate-resistant acid phosphatases: new perspectives on an old enzyme. Calcif Tissue Int 2009; 85: 465–483.
Zenger S, Ek-Rylander B, Andersson G . Biogenesis of tartrate-resistant acid phosphatase isoforms 5a and 5b in stably transfected MDA-MB-231 breast cancer epithelial cells. Biochim Biophys Acta 2010; 1803: 598–607.
Janckila AJ, Parthasarathy RN, Parthasarathy LK, Seelan RS, Hsueh YC, Rissanen J et al. Properties and expression of human tartrate-resistant acid phosphatase isoform 5a by monocyte-derived cells. J Leukoc Biol 2005; 77: 209–218.
Orlando JL, Zirino T, Quirk BJ, Averill BA . Purification and properties of the native for of the purple acid phosphatase from bovine spleen. Biochemistry 1993; 32: 117–132.
Lång P, Andersson G . Differential expression of monomeric and proteolytically processed forms of tartrate-resistant acid phosphatase in rat tissues. Cell Mol Life Sci 2005; 62: 905–918.
Hayman AR, Bune AJ, Bradley JR, Rashbass J, Cox TM . Osteoclastic tartrate-resistant acid phosphatase (Acp 5): its localization to dendritic cells and diverse murine tissues. J Histochem Cytochem 2000; 48: 219–228.
Halleen JM, Raisanen SR, Alatalo SL, Vaananen HK . Potential function for the ROS-generating activity of TRACP. J Bone Miner Res 2003; 18: 1908–1911.
Andersson G, Ek-Rylander B, Hollberg K, Ljusberg-Sjolander J, Lang P, Norgard M et al. TRACP as an osteopontin phosphatase. J Bone Miner Res 2003; 18: 1912–1915.
Ek-Rylander B, Andersson G . Osteoclast migration on phosphorylated osteopontin is regulated by endogenous tartrate-resistant acid phosphatase. Exp Cell Res 2010; 316: 443–451.
Lång P, van Harmelen V, Ryden M, Kaaman M, Parini P, Carneheim C et al. Monomeric tartrate resistant acid phosphatase induces insulin sensitive obesity. PLoS One 2008; 3: e1713.
Shih KC, Janckila AJ, Kwok CF, Ho LT, Chou YC, Chao TY . Effects of exercise on insulin sensitivity, inflammatory cytokines, and serum tartrate-resistant acid phosphatase 5a in obese Chinese male adolescents. Metabolism 2010; 59: 144–151.
Janckila AJ, Slone SP, Lear SC, Martin A, Yam LT . Tartrate-resistant acid phosphatase as an immunohistochemical marker for inflammatory macrophages. Am J Clin Pathol 2007; 127: 556–566.
Janckila AJ, Neustadt DH, Yam LT . Significance of serum TRACP in rheumatoid arthritis. J Bone Miner Res 2008; 23: 1287–1295.
Halleen JM, Alatalo SL, Janckila AJ, Woitge HW, Seibel MJ, Vaananen HK . Serum tartrate-resistant acid phosphatase 5b is a specific and sensitive marker of bone resorption. Clin Chem 2001; 47: 597–600.
Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante Jr AW . Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 2003; 112: 1796–1808.
Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 2003; 112: 1821–1830.
Curat CA, Miranville A, Sengenes C, Diehl M, Tonus C, Busse R et al. From blood monocytes to adipose tissue-resident macrophages: induction of diapedesis by human mature adipocytes. Diabetes 2004; 53: 1285–1292.
Odegaard JI, Chawla A . Mechanisms of macrophage activation in obesity-induced insulin resistance. Nat Clin Pract 2008; 4: 619–626.
Lumeng CN, DelProposto JB, Westcott DJ, Saltiel AR . Phenotypic switching of adipose tissue macrophages with obesity is generated by spatiotemporal differences in macrophage subtypes. Diabetes 2008; 57: 3239–3246.
Lumeng CN, Bodzin JL, Saltiel AR . Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest 2007; 117: 175–184.
Gordon S . Alternative activation of macrophages. Nat Rev Immunol 2003; 3: 23–35.
Mantovani A, Sica A, Sozzani S, Allavena P, Vecchi A, Locati M . The chemokine system in diverse forms of macrophage activation and polarization. Trend Immunol 2004; 25: 677–686.
Bourlier V, Zakaroff-Girard A, Miranville A, De Barros S, Maumus M, Sengenes C et al. Remodeling phenotype of human subcutaneous adipose tissue macrophages. Circulation 2008; 117: 806–815.
Zeyda M, Stulnig TM . Adipose tissue macrophages. Immunol Lett 2007; 112: 61–67.
Dahlman I, Kaaman M, Olsson T, Tan GD, Bickerton AS, Wahlen K et al. A unique role of monocyte chemoattractant protein 1 among chemokines in adipose tissue of obese subjects. J Clin Endocrinol Metab 2005; 90: 5834–5840.
Arner E, Westermark PO, Spalding KL, Britton T, Ryden M, Frisen J et al. Adipocyte turnover: relevance to human adipose tissue morphology. Diabetes 2010; 59: 105–109.
Ek-Rylander B, Barkhem T, Ljusberg J, Ohman L, Andersson KK, Andersson G . Comparative studies of rat recombinant purple acid phosphatase and bone tartrate-resistant acid phosphatase. Biochem J 1997; 321 (Part 2): 305–311.
Arvidsson E, Viguerie N, Andersson I, Verdich C, Langin D, Arner P . Effects of different hypocaloric diets on protein secretion from adipose tissue of obese women. Diabetes 2004; 53: 1966–1971.
Lofgren P, Hoffstedt J, Naslund E, Wiren M, Arner P . Prospective and controlled studies of the actions of insulin and catecholamine in fat cells of obese women following weight reduction. Diabetologia 2005; 48: 2334–2342.
Hoffstedt J, Arvidsson E, Sjolin E, Wahlen K, Arner P . Adipose tissue adiponectin production and adiponectin serum concentration in human obesity and insulin resistance. J Clin Endocrinol Metab 2004; 89: 1391–1396.
Hellmer J, Arner P, Lundin A . Automatic luminometric kinetic assay of glycerol for lipolysis studies. Anal Biochem 1989; 177: 132–137.
Kunisch E, Fuhrmann R, Roth A, Winter R, Lungershausen W, Kinne RW . Macrophage specificity of three anti-CD68 monoclonal antibodies (KP1, EBM11, and PGM1) widely used for immunohistochemistry and flow cytometry. Ann Rheum Dis 2004; 63: 774–784.
Manser P . Quality control and monitoring schemes. In Practice 1994; 16: 197–203.
Spalding KL, Arner E, Westermark PO, Bernard S, Buchholz BA, Bergmann O et al. Dynamics of fat cell turnover in humans. Nature 2008; 453: 783–787.
Moller DE . Potential role of TNF-alpha in the pathogenesis of insulin resistance and type 2 diabetes. Trends Endocrinol Metab 2000; 11: 212–217.
Hoene M, Weigert C . The role of interleukin-6 in insulin resistance, body fat distribution and energy balance. Obes Rev 2008; 9: 20–29.
Acknowledgements
We thank Eva Sjölin, Katarina Hertel, Britt-Marie Leijonhufvud, Britt-Inger Norberg and Inger Arnesjö for skilful technical assistance. This study was supported by grants from the Swedish Research Council (PA; K2008-54X-010304-42-4,GA; K2009-52X-10363-17-3), Novo Nordic Foundation, Diabetes Research Program at Karolinska Institutet, Swedish Diabetes Association, Swedish Heart and Lung Foundation and by the EU 6th and 7th Frameworks HEPADIP (LSHM-CT-2005-018734), ADAPT (HEALTH-F2-2008-201100) and COST (BM 0602), as well as the Magnus Bergwall foundation and a NOW RUBICON grant (825.07.025).
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Lång, P., Zakaroff-Girard, A., Wåhlén, K. et al. Expression and secretion of the novel adipokine tartrate-resistant acid phosphatase from adipose tissues of obese and lean women. Int J Obes 35, 1502–1510 (2011). https://doi.org/10.1038/ijo.2011.17
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DOI: https://doi.org/10.1038/ijo.2011.17
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