Skip to main content

Advertisement

Log in

Vaspin in obesity and diabetes: pathophysiological and clinical significance

  • Review
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Vaspin (visceral adipose tissue-derived serpin; serpinA12) was originally identified as an adipokine, which is predominantly secreted from visceral adipose tissue in Otsuka Long-Evans Tokushima fatty (OLETF), an animal model of obesity and type 2 diabetes. Consistent with that higher vaspin serum concentrations and increased vaspin mRNA expression in human adipose tissue were found to be associated with obesity, insulin resistance, and type 2 diabetes in humans. However, the mechanisms how vaspin secretion may be linked to deterioration of glucose metabolism and insulin sensitivity are not entirely understood. Vaspin serum concentrations show a food intake-related diurnal variation. Vaspin is also expressed in the skin, hypothalamus, pancreatic islets, and stomach. Administration of vaspin to obese mice improves glucose tolerance, insulin sensitivity, and reduces food intake. Until now molecular target(s) of vaspin and its mode of action are unknown. Thus, identification of the proteases, which are inhibited by vaspin may lead to the development of novel strategies in the treatment of obesity, diabetes and insulin resistance. This review discusses the clinical relevance of vaspin in the pathophysiology of obesity and type 2 diabetes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. E.E. Kershaw, J.S. Flier, Adipose tissue as an endocrine organ. J. Clin. Endocrinol. Metab. 89, 2548–2556 (2004)

    Article  PubMed  CAS  Google Scholar 

  2. N.E. Gulcelik, A. Usman, A. Gürlek, Role of adipocytokines in predicting the development of diabetes and its late complications. Endocrine 36, 397–403 (2009)

    Article  PubMed  CAS  Google Scholar 

  3. M. Blüher, Adipose tissue dysfunction in obesity. Exp. Clin. Endocrinol. Diabetes 117, 241–250 (2009)

    Article  PubMed  Google Scholar 

  4. H.E. Bays, “Sick fat,” metabolic disease, and atherosclerosis. Am. J. Med. 122, S26–S37 (2009)

    Article  PubMed  CAS  Google Scholar 

  5. S. Kralisch, M. Blüher, R. Paschke, M. Stumvoll, M. Fasshauer, Adipokines and adipocyte targets in the future management of obesity and the metabolic syndrome. Mini Rev. Med. Chem. 7, 39–45 (2007)

    Article  PubMed  CAS  Google Scholar 

  6. L.F. Van Gaal, I.L. Mertens, C.E. DeBlock, Mechanisms linking obesity with cardiovascular disease. Nature 444, 875–880 (2006)

    Article  PubMed  Google Scholar 

  7. M. Blüher, The inflammatory process of adipose tissue. Pediatr. Endocrinol. Rev. 6, 24–31 (2008)

    PubMed  Google Scholar 

  8. G.S. Hotamisligil, Mechanisms of TNF-alpha-induced insulin resistance. Exp. Clin. Endocrinol. Diabetes 107, 119–125 (1999)

    Article  PubMed  CAS  Google Scholar 

  9. A. Guilherme, J.V. Virbasius, V. Puri, M.P. Czech, Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes. Natl. Rev. Mol. Cell. Biol. 9, 367–377 (2008)

    Article  CAS  Google Scholar 

  10. Y. Zhang, R. Proenca, M. Maffei, M. Barone, L. Leopold, J.M. Friedman, Positional cloning of the mouse obese gene and its human homologue. Nature 372, 425–432 (1994)

    Article  PubMed  CAS  Google Scholar 

  11. R.S. Ahima, J.S. Flier, Leptin. Annu. Rev. Physiol. 62, 413–437 (2000)

    Article  PubMed  CAS  Google Scholar 

  12. H. Chen, O. Charlat, L.A. Tartaglia, E.A. Woolf, X. Weng, S.J. Ellis, N.D. Lakey, J. Culpepper, K.J. Moore, R.E. Breitbart, G.M. Duyk, R.I. Tepper, J.P. Morgenstern, Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene in db/db mice. Cell 84, 491–495 (1996)

    Article  PubMed  CAS  Google Scholar 

  13. K. Brochu-Gaudreau, C. Rehfeldt, R. Blouin, V. Bordignon, B.D. Murphy, M.F. Palin, Adiponectin action from head to toe. Endocrine 37, 11–32 (2010)

    Article  PubMed  CAS  Google Scholar 

  14. M.E. Trujillo, P.E. Scherer, Adiponectin—journey from an adipocyte secretory protein to biomarker of the metabolic syndrome. J. Intern. Med. 257, 167–175 (2005)

    Article  PubMed  CAS  Google Scholar 

  15. I. Castan-Laurell, C. Dray, C. Attané, T. Duparc, C. Knauf, P. Valet, Apelin, diabetes, and obesity. Endocrine 40, 1–9 (2011)

    Article  PubMed  CAS  Google Scholar 

  16. K. Hida, J. Wada, J. Eguchi, H. Zhang, M. Baba, A. Seida, I. Hashimoto, T. Okada, A. Yasuhara, A. Nakatsuka, K. Shikata, S. Hourai, J. Futami, E. Watanabe, Y. Matsuki, R. Hiramatsu, S. Akagi, H. Makino, Y.S. Kanwar, Visceral adipose tissue-derived serine protease inhibitor: a unique insulin-sensitizing adipocytokine in obesity. Proc. Natl. Acad. Sci. USA 102, 10610–10615 (2005)

    Article  PubMed  CAS  Google Scholar 

  17. J. Wada, Vaspin and insulin resistance. Rinsho Byori 56, 705–711 (2008)

    PubMed  CAS  Google Scholar 

  18. N. Klöting, P. Kovacs, M. Kern, J.T. Heiker, M. Fasshauer, M.R. Schön, M. Stumvoll, A.G. Beck-Sickinger, M. Blüher, Central vaspin administration acutely reduces food intake and has sustained blood glucose-lowering effects. Diabetologia 54, 1819–1823 (2011)

    Article  PubMed  Google Scholar 

  19. P.G. Gettins, Serpin structure, mechanism, and function. Chem. Rev. 102, 4751–4804 (2002)

    Article  PubMed  CAS  Google Scholar 

  20. R.H. Law, Q. Zhang, S. MacGowan, A.M. Buckle, G.A. Silverman, W. Wong, C.J. Rosado, C.G. Langendorf, R.N. Pike, P.I. Bird, J.C. Whisstock, An overview of the serpin superfamily. Genome Biol. 7, 216 (2006)

    Article  PubMed  Google Scholar 

  21. G.A. Silverman, P.I. Bird, R.W. Carrell, F.C. Church, P.B. Coughlin, P.G. Gettins, J.A. Irving, D.A. Lomas, C.J. Luke, R.W. Moyer, P.A. Pemberton, E. Remold-O’Donnell, G.S. Salvesen, J. Travis, J.C. Whisstock, The serpins are an expanding superfamily of structurally similar but functionally diverse proteins. Evolution, mechanism of inhibition, novel functions, and a revised nomenclature. J. Biol. Chem. 276, 33293–33296 (2001)

    Article  PubMed  CAS  Google Scholar 

  22. K. Kempf, B. Rose, T. Illig, W. Rathmann, K. Strassburger, B. Thorand, C. Meisinger, H.E. Wichmann, C. Herder, C. Vollmert, Vaspin (SERPINA12) genotypes and risk of type 2 diabetes: results from the MONICA/KORA studies. Exp. Clin. Endocrinol. Diabetes 118, 184–189 (2010)

    Article  PubMed  CAS  Google Scholar 

  23. N. Klöting, J. Berndt, S. Kralisch, P. Kovacs, M. Fasshauer, M.R. Schön, M. Stumvoll, M. Blüher, Vaspin gene expression in human adipose tissue: association with obesity and type 2 diabetes. Biochem. Biophys. Res. Commun. 339, 430–436 (2006)

    Article  PubMed  Google Scholar 

  24. A. Körner, M. Neef, D. Friebe, S. Erbs, J. Kratzsch, K. Dittrich, S. Blüher, T.M. Kapellen, P. Kovacs, M. Stumvoll, M. Blüher, W. Kiess, Vaspin is related to gender, puberty and deteriorating insulin sensitivity in children. Int. J. Obes. (Lond.) 35, 578–586 (2011)

    Article  Google Scholar 

  25. J.N. Fain, B. Buehrer, S.W. Bahouth, D.S. Tichansky, A.K. Madan, Comparison of messenger RNA distribution for 60 proteins in fat cells vs the nonfat cells of human omental adipose tissue. Metabolism 57, 1005–1015 (2008)

    Article  PubMed  CAS  Google Scholar 

  26. U. Meyer-Hoffert, Reddish, scaly, and itchy: how proteases and their inhibitors contribute to inflammatory skin diseases. Arch. Immunol. Ther. Exp. 57, 345–354 (2009)

    Article  CAS  Google Scholar 

  27. B.S. Youn, N. Klöting, J. Kratzsch, N. Lee, J.W. Park, E.S. Song, K. Ruschke, A. Oberbach, M. Fasshauer, M. Stumvoll, M. Blüher, Serum vaspin concentrations in human obesity and type 2 diabetes. Diabetes 57, 372–377 (2008)

    Article  PubMed  CAS  Google Scholar 

  28. C. von Loeffelholz, M. Möhlig, A.M. Arafat, F. Isken, J. Spranger, K. Mai, H.S. Randeva, A.F. Pfeiffer, M.O. Weickert, Circulating vaspin is unrelated to insulin sensitivity in a cohort of nondiabetic humans. Eur. J. Endocrinol. 162, 507–513 (2010)

    Article  Google Scholar 

  29. G. Aust, O. Richter, S. Rohm, C. Kerner, J. Hauss, N. Klöting, K. Ruschke, B.S. Youn, M. Blüher, Vaspin serum concentrations in patients with carotid stenosis. Atherosclerosis 204, 262–266 (2009)

    Article  PubMed  CAS  Google Scholar 

  30. A. Handisurya, M. Riedl, G. Vila, C. Maier, M. Clodi, T. Prikoszovich, B. Ludvik, G. Prager, A. Luger, A. Kautzky-Willer, Serum vaspin concentrations in relation to insulin sensitivity following RYGB-induced weight loss. Obes. Surg. 20, 198–203 (2010)

    Article  PubMed  Google Scholar 

  31. B.L. Tan, D. Heutling, J. Chen, S. Farhatullah, R. Adya, S.D. Keay, C.R. Kennedy, H. Lehnert, H.S. Randeva, Metformin decreases the adipokine vaspin in overweight women with polycystic ovary syndrome concomitant with improvement in insulin sensitivity and a decrease in insulin resistance. Diabetes 57, 1501–1507 (2008)

    Article  PubMed  CAS  Google Scholar 

  32. N.E. Gulcelik, J. Karakaya, A. Gedik, A. Usman, A. Gurlek, Serum vaspin levels in type 2 diabetic women in relation to microvascular complications. Eur. J. Endocrinol. 160, 65–70 (2009)

    Article  PubMed  CAS  Google Scholar 

  33. J. Seeger, M. Ziegelmeier, A. Bachmann, U. Lössner, J. Kratzsch, M. Blüher, M. Stumvoll, M. Fasshauer, Serum levels of the adipokine vaspin in relation to metabolic and renal parameters. J. Clin. Endocrinol. Metab. 93, 247–251 (2008)

    Article  PubMed  CAS  Google Scholar 

  34. N.P. Kadoglou, A. Kapelouzou, H. Tsanikidis, I. Vitta, C.D. Liapis, N. Sailer, Effects of rosiglitazone/metformin fixed-dose combination therapy and metformin monotherapy on serum vaspin, adiponectin and IL-6 levels in drug-naïve patients with type 2 diabetes. Exp. Clin. Endocrinol. Diabetes 119, 63–68 (2011)

    Article  PubMed  CAS  Google Scholar 

  35. S. Akbarzadeh, I. Nabipour, S.M. Jafari, A. Movahed, N. Motamed, M. Assadi, N. Hajian, Serum visfatin and vaspin levels in normoglycemic first-degree relatives of Iranian patients with type 2 diabetes mellitus. Diabetes Res. Clin. Pract. (2011). doi:10.1016/j.diabres.2011.10.004

  36. N. Cinar, N.E. Gülçelik, K. Aydín, S. Akín, A. Usman, A. Gürlek, Serum vaspin levels in hypothyroid patients. Eur. J. Endocrinol. 165, 563–569 (2011)

    Article  PubMed  CAS  Google Scholar 

  37. J.A. Lee, H.S. Park, Y.S. Song, Y.J. Jang, J.H. Kim, Y.J. Lee, Y.S. Heo, Relationship between vaspin gene expression and abdominal fat distribution of Korean women. Endocr. J. 8, 639–646 (2011)

    Article  Google Scholar 

  38. N. Klöting, M. Fasshauer, A. Dietrich, P. Kovacs, M.R. Schön, M. Kern, M. Stumvoll, M. Blüher, Insulin-sensitive obesity. Am. J. Physiol. Endocrinol. Metab. 299, E506–E515 (2010)

    Article  PubMed  Google Scholar 

  39. H.L. Li, W.H. Peng, S.T. Cui, H. Lei, Y.D. Wei, W.M. Li, Y.W. Xu, Vaspin plasma concentrations and mRNA expressions in patients with stable and unstable angina pectoris. Clin. Chem. Lab. Med. 49, 1547–1554 (2011)

    Article  PubMed  CAS  Google Scholar 

  40. N.P. Kadoglou, A. Gkontopoulos, A. Kapelouzou, G. Fotiadis, E.K. Theofilogiannakos, G. Kottas, S. Lampropoulos, Serum levels of vaspin and visfatin in patients with coronary artery disease—Kozani study. Clin. Chim. Acta 412, 48–52 (2011)

    Article  PubMed  CAS  Google Scholar 

  41. Y. Yilmaz, R. Kurt, A. Gurdal, Y.O. Alahdab, O. Yonal, E. Senates, N. Polat, F. Eren, N. Imeryuz, H. Oflaz, Circulating vaspin levels and epicardial adipose tissue thickness are associated with impaired coronary flow reserve in patients with nonalcoholic fatty liver disease. Atherosclerosis 217, 125–129 (2011)

    Article  PubMed  CAS  Google Scholar 

  42. S.G. Spiroglou, C.G. Kostopoulos, J.N. Varakis, H.H. Papadaki, Adipokines in periaortic and epicardial adipose tissue: differential expression and relation to atherosclerosis. J. Atheroscler. Thromb. 17, 115–130 (2010)

    Article  PubMed  CAS  Google Scholar 

  43. C.H. Jung, W.J. Lee, J.Y. Hwang, S.M. Seol, Y.M. Kim, Y.L. Lee, J.Y. Park, Vaspin protects vascular endothelial cells against free fatty acid-induced apoptosis through a phosphatidylinositol 3-kinase/Akt pathway. Biochem. Biophys. Res. Commun. 413, 264–269 (2011)

    Article  PubMed  CAS  Google Scholar 

  44. N.P. Kadoglou, I.S. Vrabas, A. Kapelouzou, S. Lampropoulos, N. Sailer, A. Kostakis, C.D. Liapis, Impact of atorvastatin on serum vaspin levels in hypercholesterolemic patients with moderate cardiovascular risk. Regul. Pept. 170, 57–61 (2011)

    Article  PubMed  CAS  Google Scholar 

  45. J.K. Cho, T.K. Han, H.S. Kang, Combined effects of body mass index and cardio/respiratory fitness on serum vaspin concentrations in Korean young men. Eur. J. Appl. Physiol. 108, 347–353 (2010)

    Article  PubMed  Google Scholar 

  46. S.M. Kim, G.J. Cho, M. Yannakoulia, T.G. Hwang, I.H. Kim, E.K. Park, C.S. Mantzoros, Lifestyle modification increases circulating adiponectin concentrations but does not change vaspin concentrations. Metabolism 60, 1294–1299 (2011)

    Article  PubMed  CAS  Google Scholar 

  47. A. Oberbach, K. Kirsch, S. Lehmann, N. Schlichting, M. Fasshauer, K. Zarse, M. Stumvoll, M. Ristow, M. Blüher, P. Kovacs, Serum vaspin concentrations are decreased after exercise-induced oxidative stress. Obes. Facts 3, 328–331 (2010)

    Article  PubMed  CAS  Google Scholar 

  48. M. Ristow, K. Zarse, A. Oberbach, N. Klöting, M. Birringer, M. Kiehntopf, M. Stumvoll, C.R. Kahn, M. Blüher, Antioxidants prevent health-promoting effects of physical exercise in humans. Proc. Natl. Acad. Sci. USA 106, 8665–8670 (2009)

    Article  PubMed  CAS  Google Scholar 

  49. A. Tönjes, M. Fasshauer, J. Kratzsch, M. Stumvoll, M. Blüher, Adipokine pattern in subjects with impaired fasting glucose and impaired glucose tolerance in comparison to normal glucose tolerance and diabetes. PLoS ONE 5, e13911 (2010)

    Article  PubMed  Google Scholar 

  50. E. Jeong, B.S. Youn, D.W. Kim, E.H. Kim, J.W. Park, C. Namkoong, J.Y. Jeong, S.Y. Yoon, J.Y. Park, K.U. Lee, M.S. Kim, Circadian rhythm of serum vaspin in healthy male volunteers: relation to meals. J. Clin. Endocrinol. Metab. 95, 1869–1875 (2010)

    Article  PubMed  CAS  Google Scholar 

  51. L. Brunetti, C. Di Nisio, L. Recinella, A. Chiavaroli, S. Leone, C. Ferrante, G. Orlando, M. Vacca, Effects of vaspin, chemerin and omentin-1 on feeding behavior and hypothalamic peptide gene expression in the rat. Peptides 32, 1866–1871 (2011)

    Article  PubMed  CAS  Google Scholar 

  52. L.J. Aronne, T. Wadden, K.K. Isoldi, K.A. Woodworth, When prevention fails: obesity treatment strategies. Am. J. Med. 122, S24–S32 (2009)

    Article  PubMed  Google Scholar 

  53. I. Shai, D. Schwarzfuchs, Y. Henkin, D.R. Shahar, S. Witkow, I. Greenberg, R. Golan, D. Fraser, A. Bolotin, H. Vardi, O. Tangi-Rozental, R. Zuk-Ramot, B. Sarusi, D. Brickner, Z. Schwartz, E. Sheiner, R. Marko, E. Katorza, J. Thiery, G.M. Fiedler, M. Blüher, M. Stumvoll, M.J. Stampfer, Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. N. Engl. J. Med. 359, 229–241 (2008)

    Article  PubMed  CAS  Google Scholar 

  54. M. Blüher, A. Rudich, N. Klöting, R. Golan, Y. Henkin, E. Rubin, D. Schwarzfuchs, Y. Gepner, M. J. Stampfer, M. Fiedler, J. Thiery, M. Stumvoll, I. Shai, Two patterns of adipokine and other biomarker dynamics in a long term weight loss intervention. Diabetes Care (2011, in press)

  55. E. Koiou, K. Tziomalos, K. Dinas, I. Katsikis, E. Kalaitzakis, D. Delkos, E.A. Kandaraki, D. Panidis, The effect of weight loss and treatment with metformin on serum vaspin levels in women with polycystic ovary syndrome. Endocr. J. 58, 237–246 (2011)

    Article  PubMed  CAS  Google Scholar 

  56. G.A. Martos-Moreno, J. Kratzsch, A. Körner, V. Barrios, F. Hawkins, W. Kiess, J. Argente, Serum visfatin and vaspin levels in prepubertal children: effect of obesity and weight loss after behavior modifications on their secretion and relationship with glucose metabolism. Int. J. Obes. (Lond.) 35, 1355–1362 (2011)

    Article  CAS  Google Scholar 

  57. H.M. Chang, H.J. Lee, H.S. Park, J.H. Kang, K.S. Kim, Y.S. Song, Y.J. Jang, Effects of weight reduction on serum vaspin concentrations in obese subjects: modification by insulin resistance. Obesity 18, 2105–2110 (2010)

    Article  PubMed  CAS  Google Scholar 

  58. E.S. Kang, F. Magkos, E. Sienkiewicz, C.S. Mantzoros, Circulating vaspin and visfatin are not affected by acute or chronic energy deficiency or leptin administration in humans. Eur. J. Endocrinol. 164, 911–917 (2011)

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Matthias Blüher.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Blüher, M. Vaspin in obesity and diabetes: pathophysiological and clinical significance. Endocrine 41, 176–182 (2012). https://doi.org/10.1007/s12020-011-9572-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-011-9572-0

Keywords

Navigation