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Depot-specific regulation of autotaxin with obesity in human adipose tissue

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Abstract

Autotaxin (ATX) is a lysophospholipase D involved in synthesis of a bioactive mediator: lysophosphatidic. ATX is abundantly produced by adipocytes and exerts a negative action on adipose tissue expansion. In both mice and humans, ATX expression increases with obesity in association with insulin resistance. In the present study, fat depot-specific regulation of ATX was explored in human. ATX mRNA expression was quantified in visceral and subcutaneous adipose tissue in obese (BMI > 40 kg/m2; n = 27) and non-obese patients (BMI < 25 kg/m2; n = 10). Whatever the weight status of the patients is, ATX expression was always higher (1.3- to 6-fold) in subcutaneous than in visceral fat. Nevertheless, visceral fat ATX was significantly higher (42 %) in obese than in non-obese patients, whereas subcutaneous fat ATX remained unchanged. In obese patients, visceral fat ATX expression was positively correlated with diastolic arterial blood pressure (r = 0.67; P = 0.001). This correlation was not observed with subcutaneous fat ATX. Visceral fat ATX was mainly correlated with leptin (r = 0.60; P = 0.001), inducible nitric oxide synthase (r = 0.58; P = 0,007), and apelin receptor (r = 0.50; P = 0.007). These correlations were not observed with subcutaneous fat ATX. These results reveal that obesity-associated upregulation of human adipose tissue ATX is specific to the visceral fat depot.

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References

  1. Achike FI, To NH, Wang H, Kwan CY (2011) Obesity, metabolic syndrome, adipocytes and vascular function: a holistic viewpoint. Clin Exp Pharmacol Physiol 38:1–10

    Article  PubMed  CAS  Google Scholar 

  2. Boucher J, Quilliot D, Praderes JP, Simon MF, Gres S, Guigne C, Prevot D, Ferry G, Boutin JA, Carpene C, Valet P, Saulnier-Blache JS (2005) Potential involvement of adipocyte insulin resistance in obesity-associated up-regulation of adipocyte lysophospholipase D/autotaxin expression. Diabetologia 48:569–577

    Article  PubMed  CAS  Google Scholar 

  3. Boutin JA, Ferry G (2009) Autotaxin. Cell Mol Life Sci 66:3009–3021

    Article  PubMed  CAS  Google Scholar 

  4. Dusaulcy R, Rancoule C, Gres S, Wanecq E, Colom A, Guigne C, van Meeteren LA, Moolenaar WH, Valet P, Saulnier-Blache JS (2011) Adipose-specific disruption of autotaxin enhances nutritional fattening and reduces plasma lysophosphatidic acid. J Lipid Res 52:1247–1255

    Article  PubMed  CAS  Google Scholar 

  5. Ferry G, Moulharat N, Pradere JP, Desos P, Try A, Genton A, Giganti A, Beucher-Gaudin M, Lonchampt M, Bertrand M, Saulnier-Blache JS, Tucker GC, Cordi A, Boutin JA (2008) S32826, a nanomolar inhibitor of autotaxin: discovery, synthesis and applications as a pharmacological tool. J Pharmacol Exp Ther 327:809–819

    Article  PubMed  CAS  Google Scholar 

  6. Ferry G, Tellier E, Try A, Gres S, Naime I, Simon MF, Rodriguez M, Boucher J, Tack I, Gesta S, Chomarat P, Dieu M, Raes M, Galizzi JP, Valet P, Boutin JA, Saulnier-Blache JS (2003) Autotaxin is released from adipocytes, catalyzes lysophosphatidic acid synthesis, and activates preadipocyte proliferation. Up-regulated expression with adipocyte differentiation and obesity. J Biol Chem 278:18162–18169

    Article  PubMed  CAS  Google Scholar 

  7. Fotopoulou S, Oikonomou N, Grigorieva E, Nikitopoulou I, Paparountas T, Thanassopoulou A, Zhao Z, Xu Y, Kontoyiannis DL, Remboutsika E, Aidinis V (2010) ATX expression and LPA signalling are vital for the development of the nervous system. Dev Biol 339:451–464

    Article  PubMed  CAS  Google Scholar 

  8. Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18:499–502

    PubMed  CAS  Google Scholar 

  9. Gesta S, Simon MF, Rey A, Sibrac D, Girard A, Lafontan M, Valet P, Saulnier-Blache JS (2002) Secretion of a lysophospholipase D activity by adipocytes: involvement in lysophosphatidic acid synthesis. J Lipid Res 43:904–910

    PubMed  CAS  Google Scholar 

  10. Jeon ES, Moon HJ, Lee MJ, Song HY, Kim YM, Cho M, Suh DS, Yoon MS, Chang CL, Jung JS, Kim JH (2008) Cancer-derived lysophosphatidic acid stimulates differentiation of human mesenchymal stem cells to myofibroblast-like cells. Stem Cells 26:789–797

    Article  PubMed  CAS  Google Scholar 

  11. Lau TT, Wang DA (2010) Stromal cell-derived factor-1 (SDF-1): homing factor for engineered regenerative medicine. Expert Opin Biol Ther 11:189–197

    Article  Google Scholar 

  12. Liu S, Murph M, Panupinthu N, Mills GB (2009) ATX-LPA receptor axis in inflammation and cancer. Cell Cycle 8:3695–3701

    Article  PubMed  CAS  Google Scholar 

  13. Pradere JP, Tarnus E, Gres S, Valet P, Saulnier-Blache JS (2007) Secretion and lysophospholipase D activity of autotaxin by adipocytes are controlled by N-glycosylation and signal peptidase. Biochim Biophys Acta 1771:93–102

    Article  PubMed  CAS  Google Scholar 

  14. Rancoule C, Pradere JP, Gonzalez J, Klein J, Valet P, Bascands JL, Schanstra JP, Saulnier-Blache JS (2011) Lysophosphatidic acid-1-receptor targeting agents for fibrosis. Expert Opin Investig Drugs 20:657–667

    Article  PubMed  CAS  Google Scholar 

  15. Simon MF, Daviaud D, Pradere JP, Gres S, Guigne C, Wabitsch M, Chun J, Valet P, Saulnier-Blache JS (2005) Lysophosphatidic acid inhibits adipocyte differentiation via lysophosphatidic acid 1 receptor-dependent down-regulation of peroxisome proliferator-activated receptor gamma2. J Biol Chem 280:14656–14662

    Article  PubMed  CAS  Google Scholar 

  16. Tanaka M, Okudaira S, Kishi Y, Ohkawa R, Iseki S, Ota M, Noji S, Yatomi Y, Aoki J, Arai H (2006) Autotaxin stabilizes blood vessels and is required for embryonic vasculature by producing lysophosphatidic acid. J Biol Chem 281:25822–25830

    Article  PubMed  CAS  Google Scholar 

  17. Tokumura A, Kume T, Fukuzawa K, Tsukatani H (1981) Cardiovascular effects of lysophosphatidic acid and its structural analogs in rats. J Pharmacol Exp Ther 219:219–224

    PubMed  CAS  Google Scholar 

  18. van Meeteren LA, Moolenaar WH (2007) Regulation and biological activities of the autotaxin-LPA axis. Prog Lipid Res 46:145–160

    Article  PubMed  Google Scholar 

  19. van Meeteren LA, Ruurs P, Stortelers C, Bouwman P, van Rooijen MA, Pradere JP, Pettit TR, Wakelam MJ, Saulnier-Blache JS, Mummery CL, Moolenaar WH, Jonkers J (2006) Autotaxin, a secreted lysophospholipase D, is essential for blood vessel formation during development. Mol Cell Biol 26:5015–5022

    Article  PubMed  Google Scholar 

  20. Xu YJ, Aziz OA, Bhugra P, Arneja AS, Mendis MR, Dhalla NS (2003) Potential role of lysophosphatidic acid in hypertension and atherosclerosis. Can J Cardiol 19:1525–1536

    PubMed  CAS  Google Scholar 

  21. Xu YJ, Rathi SS, Zhang M, Bhugra P, Dhalla NS (2002) Mechanism of the positive inotropic effect of lysophosphatidic acid in rat heart. J Cardiovasc Pharmacol Ther 7:109–115

    Article  PubMed  CAS  Google Scholar 

  22. Yuelling LM, Fuss B (2008) Autotaxin (ATX): a multi-functional and multi-modular protein possessing enzymatic lysoPLD activity and matricellular properties. Biochim Biophys Acta 1781:525–530

    Article  PubMed  CAS  Google Scholar 

  23. Zhou Z, Subramanian P, Sevilmis G, Globke B, Soehnlein O, Karshovska E, Megens R, Heyll K, Chun J, Saulnier-Blache JS, Reinholz M, van Zandvoort M, Weber C, Schober A (2011) Lipoprotein-derived lysophosphatidic acid promotes atherosclerosis by releasing CXCL1 from the endothelium. Cell Metab 13:592–600

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by grants from the INSERM and the Fondation pour la Recherche Médicale (grant #DRM20101220459). Chloé Rancoule and Rodolphe Dusaulcy were supported by a grant from the Ministère de l'Education Nationale de la Recherche et de la Technologie (France).

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Authors and Affiliations

  1. Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Inserm U1048, Université Paul Sabatier, Equipe n°3 (Bat L4), 1 Avenue Jean Poulhès, BP 84225, 31432, Toulouse Cedex 4, France

    Chloé Rancoule, Rodolphe Dusaulcy, Karine Tréguer, Sandra Grès, Charlotte Guigné, Philippe Valet & Jean Sébastien Saulnier-Blache

  2. Service de Diabétologie, Maladies Métaboliques et Nutrition, Hôpital J. d’Arc, CHU de Nancy, Nancy, France

    Didier Quilliot

Authors
  1. Chloé Rancoule
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  2. Rodolphe Dusaulcy
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  3. Karine Tréguer
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  4. Sandra Grès
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  5. Charlotte Guigné
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  6. Didier Quilliot
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  7. Philippe Valet
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  8. Jean Sébastien Saulnier-Blache
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Correspondence to Jean Sébastien Saulnier-Blache.

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Rancoule, C., Dusaulcy, R., Tréguer, K. et al. Depot-specific regulation of autotaxin with obesity in human adipose tissue. J Physiol Biochem 68, 635–644 (2012). https://doi.org/10.1007/s13105-012-0181-z

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  • DOI: https://doi.org/10.1007/s13105-012-0181-z

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