Skip to main content
SpringerLink
Log in

Vaspin gene in rat adipose tissue: relation to obesity-induced insulin resistance

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Visceral adipose fat has been claimed to be the link between obesity and insulin resistance through the released adipokines. This study aimed to assess the expression of vaspin as one of the recent adipokines in rats abdominal subcutaneous and visceral fat in diet-induced obese (DIO) and in DIO performing 3 weeks swimming exercise (DIO + EXE) compared to control and control + exercise (C + EXE) groups. Vaspin mRNA and protein expression assessed using RT-PCR and Western blotting analysis revealed vaspin expression in DIO and DIO + EXE but not in controls groups. In DIO group, visceral vaspin expression was higher than in that of subcutaneous fat and was positively correlated with body weight. Upregulation of visceral vaspin expression in DIO was concomitant with the development of insulin resistance (increase in fasting serum insulin and HOMA-IR) and rise in serum leptin level. Unchanged visceral vaspin mRNA in DIO + EXE rats, with significant improvements of insulin resistance parameters and serum leptin compared to DIO group was found. In conclusion, increased visceral vaspin expression in obesity was associated with insulin resistance. Further investigations into the molecular links between vaspin and obesity may unravel innovative therapeutic strategies in people affected by obesity-linked insulin resistance, metabolic syndrome, and type 2 diabetes.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

BMI:

Body mass index

DIO:

Diet-induced obese

EXE:

Exercise

FFAs:

Free fatty acids

HOMA-IR:

Homeostasis model assessment of insulin resistance

IL:

Interleukin

MCP-1:

Macrophage chemoattractant protein-1

PAI-1:

Plasminogen-activated inhibitor-1

ROS:

Reactive oxygen species

rhVaspin:

Recombinant human vaspin

Serpin:

Serine protease inhibitor

SBP:

Systolic blood pressure

TGs:

Triglycerides

TNF-α:

Tumor necrosis factor-α

Vaspin:

Visceral adipose tissue-derived serine protease inhibitor

WATs:

White adipose tissues

References

  1. James PT (2004) Obesity: the worldwide epidemic. Clin Dermatol 4:276–280

    Article  Google Scholar 

  2. Carey V, Walters E, Colditz G (1997) Body fat distribution and risk of non-insulin-dependent diabetes in women. Am J Epidemiol 145:614–619

    Article  PubMed  CAS  Google Scholar 

  3. Seida A, Wada J, Kunitomi M, Tsuchiyama Y, Miyatake N, Fujii M et al (2003) Serum βFGF levels are reduced in Japanese overweight men and restored by a 6-month exercise education. Int J Obes Relat Metab Disord 27:1325–1331

    Article  PubMed  CAS  Google Scholar 

  4. Despres JP, Moorjani S, Lupien PJ, Tremblay A, Nadeau A, Bouchard C (1990) Regional distribution of body fat, plasma lipoproteins, and cardiovascular disease. Arteriosclerosis 10:497–511

    Article  PubMed  CAS  Google Scholar 

  5. Boden G (1997) Role of fatty acids in the pathogenesis of insulin resistance and NIDDM. Diabetes 46:3–10

    Article  PubMed  CAS  Google Scholar 

  6. Nielsen S, Guo ZK, Johnson CM, Hensrud DD, Jensen MD (2004) Splanchnic lipolysis in human obesity. J Clin Invest 113:1582–1588

    PubMed  CAS  Google Scholar 

  7. Klein S (2004) The case of visceral fat: argument for the defense. J Clin Invest 113:1530–1532

    PubMed  CAS  Google Scholar 

  8. Goodpaster BH (2005) Skeletal muscle lipid and its association with insulin resistance: what is the role for exercise? Exerc Sport Sci Rev 33:150–154

    Article  PubMed  Google Scholar 

  9. Calles-Escandon J, Goran MI, O’Connell M, Nair KS, Danforth E Jr (1996) Exercise increases fat oxidation at rest unrelated to changes in energy balance or lipolysis. Am J Physiol 270:E1009–E1014

    PubMed  CAS  Google Scholar 

  10. Trayhurn P (2005) Endocrine and signaling role of adipose tissue: new perspectives on fat. Acta Physiol Scand 184:285–293

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  12. Scherer PE, Williams S, Fogliano M, Baldini G, Lodish HF (1995) A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem 270:26746–26749

    Article  PubMed  CAS  Google Scholar 

  13. Samad F, Yamamoto K, Loskutoff DJ (1996) Distribution and regulation of plasminogen activator inhibitor-1 in murine adipose tissue in vivo. Induction by tumor necrosis factor-# and lipopolysaccharide. J Clin Invest 97:37–46

    Article  PubMed  CAS  Google Scholar 

  14. Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM et al (2001) The hormone resistin links obesity to diabetes. Nature 409:307–312

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  16. Hida K, Wada J, Eguchi J, Zhang H, Baba M, Seida A et al (2005) Visceral adipose tissue-derived serine protease inhibitor: a unique insulin-sensitizing adipocytokine in obesity. Proc Natl Acad Sci USA 102:10610–10615

    Article  PubMed  CAS  Google Scholar 

  17. Klöting N, Kovacs P, Kern M, Heiker JT, Fasshauer M, Scho¨n MR et al (2011) Central vaspin administration acutely reduces food intake and has sustained blood glucose-lowering effects. Diabetologia 54:1819–1823

    Article  PubMed  Google Scholar 

  18. Körner A, Neef M, Friebe D, Erbs S, Kratzsch J, Dittrich K et al (2011) Vaspin is related to gender, puberty and deteriorating insulin sensitivity in children. Int J Obes (Lond) 35:578–586

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  20. Klöting N, Berndt J, Kralisch S, Kovacs P, Fasshauer M, Schon MR et al (2006) Vaspin gene expression in human adipose tissue: association with obesity and type 2 diabetes. Biochem Biophys Res Commun 339:430–436

    Article  PubMed  Google Scholar 

  21. Youn BS, Klöting N, Kratzsch J, Lee N, Park JW, Song ES et al (2008) Serum vaspin concentrations in human obesity and type 2 diabetes. Diabetes 57:372–377

    Article  PubMed  CAS  Google Scholar 

  22. Wada J (2008) Vaspin: a novel serpin with insulin-sensitizing effects. Exp Opin Investig Drugs 17(3):327–333

    Article  CAS  Google Scholar 

  23. Ward FW, Coates ME (1987) Dietary fat and N-nitrosation in the rat. Br J Nutr 58:221–231

    Article  PubMed  CAS  Google Scholar 

  24. Lajoie C, Calderone A, Trudeau F, Lavoie N, Massicotte G, Gagnon S et al (2004) Exercise training attenuated the PKB and GSK-3 dephosphorylation in the myocardium of ZDF rats. J Appl Physiol 96:1606–1612

    Article  PubMed  CAS  Google Scholar 

  25. Zhang QJ, Li QX, Zhang HF, Zhang KR, Guo WY, Wang HC et al (2007) Swim training sensitizes myocardial response to insulin: role of Akt-dependent eNOS activation. Cardiovasc Res 75(2):369–380

    Article  PubMed  CAS  Google Scholar 

  26. Dobrian A, Michael JD, Russell LP, Thomas JL (2000) Development of hypertension in a rat model of diet-induced obesity. Hypertension 35:1009–1019

    Article  PubMed  CAS  Google Scholar 

  27. Whittington KB, Solomon SS, Lu ZN, Selawry HP (1991) Islet allografts in the cryptorchid testes of spontaneously diabetic BB/Wor dp rats: response to glucose, glipizide, and arginine. Endocrinology 128:2671–2677

    Article  PubMed  CAS  Google Scholar 

  28. Axen KV, Dikeakos A, Sclafani A (2003) High dietary fat promotes syndrome X in non obese rats. J Nutr 133:2244–2249

    PubMed  CAS  Google Scholar 

  29. Kekow J, Ulrichs K, Muller-Ruchholtz W, Gross WL (1988) Measurement of rat insulin-ELISA with increased sensitivity, high accuracy and greater practicability than established radioimmunoassay. Diabetes 37:321–326

    Article  PubMed  CAS  Google Scholar 

  30. Greenbaum CJ, Cuthbertson D, Krischer JP, Diabetes Prevention Trial of Type 1 Diabetes Study Group (2001) Type 1 diabetes manifested solely by 2-h oral glucose tolerance test criteria. Diabetes 50:470–476

    Article  PubMed  CAS  Google Scholar 

  31. Cruickshank JK, Heald AH, Anderson S, Cade JE, Sampayo J, Riste LK et al (2001) Epidemiology of the insulin-like growth factor system in three ethnic groups. Am J Epidemiol 154:504–513

    Article  PubMed  CAS  Google Scholar 

  32. Freeman NM, Walker S, Vrana K (1999) Quantitative RT-PCR: pitfalls and potential. Biotechniques 26:112–125

    PubMed  CAS  Google Scholar 

  33. Morsi WG, Shaker OG, Ismail EF, Ahmed HH, El-Serafi TI, Maklady FA et al (2006) HO-1 and VGEF gene expression in human arteries with advanced atherosclerosis. Clin Biochem 39:1057–1062

    Article  PubMed  CAS  Google Scholar 

  34. Norusis M (1997) SPSS 7.5 Guide to data analysis, Simon and Schuster Company, Upper Saddle River, New Jersey

  35. Bonora EF, Formentini G, Calcaterra F (2002) HOMA estimated insulin resistance is an independent predictor of cardiovascular disease in type 2 diabetic subjects: prospective data from the Verona diabetes study. Diabetes Care 25:1135–1141

    Article  PubMed  Google Scholar 

  36. Freedland ES (2004) Role of a critical visceral adipose tissue threshold (CVATT) in metabolic syndrome: implications for controlling dietary carbohydrates: a review. Nutr Metab 1:12–22

    Article  Google Scholar 

  37. Linder K, Arner P, Flores-Morales A, Tollet-Egnell P (2004) Differentially expressed genes in visceral or subcutaneous adipose tissue of obese men and women. J Lipid Res 45:148–154

    Article  PubMed  CAS  Google Scholar 

  38. Van Harmelen V, Dicker A, Ryden M, Hauner H, Lonnqvist F, Naslund E et al (2002) Increased lipolysis and decreased leptin production by human omental as compared with subcutaneous preadipocytes. Diabetes 51:2029–2036

    Article  PubMed  Google Scholar 

  39. Lafontan M (2004) Fat cells: afferent and efferent messages define new approaches to treat obesity. Annu Rev Pharmacol Toxicol 45:119–146

    Article  Google Scholar 

  40. Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ et al (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112:1821–1830

    PubMed  CAS  Google Scholar 

  41. Park KG, Park KS, Kim MJ, Kim HS, Suh YS, Ahn JD et al (2004) Relationship between serum adiponectin and leptin concentrations and body fat distribution. Diabetes Res Clin Pract 63:135–142

    Article  PubMed  CAS  Google Scholar 

  42. Trujillo ME, Scherer PE (2005) Adiponectin: journey from an adipocyte secretory protein to biomarker of the metabolic syndrome. J Intern Med 257:167–175

    Article  PubMed  CAS  Google Scholar 

  43. Blüher M (2012) Vaspin in obesity and diabetes: pathophysiological and clinical significance. Endocrine 41:176–182

    Article  PubMed  Google Scholar 

  44. Vera ER, Battell ML, Bhanot S, McNeill JH (2002) Effects of age and anesthetic on plasma glucose and insulin levels and insulin sensitivity in spontaneously hypertensive and Wistar rats. Can J Physiol Pharmacol 80:962–970

    Article  PubMed  CAS  Google Scholar 

  45. Lee KH, Ko BH, Paik JH, Jung KH, Choe YH, Choi Y et al (2005) Effects of anesthetic agents and fasting duration on 18F-FDG biodistribution and insulin levels in tumor-bearing mice. J Nucl Med 46:1531–1536

    PubMed  CAS  Google Scholar 

  46. Johansen O, Vaaler S, Jorde R, Reikeras O (1994) Increased plasma glucose levels after Hypnorm anaesthesia, but not after pentobarbital anaesthesia in rats. Lab Anim 28:244–248

    Article  PubMed  CAS  Google Scholar 

  47. Pérez C, Fernández-Galaz C, Fernández-Agulló T, Arribas C, Andrés A, Ros M, Carrascosa JM et al (2004) Leptin impairs insulin signaling in rat adipocytes. Diabetes 53:347–353

    Article  PubMed  Google Scholar 

  48. Kamohara S, Burcelin R, Halaas JL, Friedman JM, Charron MJ (1997) Acute stimulation of glucose metabolism in mice by leptin treatment. Nature 389:374–377

    Article  PubMed  CAS  Google Scholar 

  49. Petersen KF, Oral EA, Dufour S, Befroy D, Ariyan C, Yu C et al (2002) Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy. J Clin Invest 109:1345–1350

    PubMed  CAS  Google Scholar 

  50. Fukui M, Kitagawa Y, Nakamura N, Yoshikawa T (2002) Response to Öncül. Diabetes Care 25:1900–1901

    Article  PubMed  Google Scholar 

  51. Cohen B, Novick D, Rubinstein M (1996) Modulation of insulin activities by leptin. Science 274:1185–1188

    Article  PubMed  CAS  Google Scholar 

  52. Girard J (1997) Is leptin the link between obesity and insulin resistance? Diabetes Metab 23(Suppl 3):16–24

    PubMed  CAS  Google Scholar 

  53. Pijl H, Toornvliet AC, Meinders AE (1996) Serum leptin in normal-weight and obese humans. N Engl J Med 334(23):1544 (Comment on N Engl J Med 334(5):292–295)

    Google Scholar 

  54. Chen H, Charlat O, Tartaglia LA, Woolf EA, Weng X, Ellis SJ et al (1996) 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

    Article  PubMed  CAS  Google Scholar 

  55. Kim SM, Cho GJ, Yannakoulia M, Hwang TG, Kim IH, Park EK et al (2011) Lifestyle modification increases circulating adiponectin concentrations but does not change vaspin concentrations. Metabolism 60:1294–1299

    Article  PubMed  CAS  Google Scholar 

  56. Bloem CJ, Chang AM (2008) Short-term exercise improves beta-cell function and insulin resistance in older people with impaired glucose tolerance. J Clin Endocrinol Metab 93:387–392

    Article  PubMed  CAS  Google Scholar 

  57. Skalicky J, Muzakova V, Kandar R, Meloun M, Rousar T, Palicka V (2008) Evaluation of oxidative stress and inflammation in obese adults with metabolic syndrome. Clin Chem Lab Med 46:499–505

    Article  PubMed  CAS  Google Scholar 

  58. Oberbach A, Kirsch K, Lehmann S, Schlichting N, Fasshauer M, Zarse K et al (2010) Serum vaspin concentrations are decreased after exercise-induced oxidative stress. Obes Facts 3:328–331

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge the financial assistance provided by the Faculty of Medicine, Cairo University.

Conflict of interest

The authors declared that there is no conflict of interest.

Author information

Authors and Affiliations

  1. Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Cairo, Egypt

    Olfat G. Shaker

  2. Biochemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Eini Street, Cairo, 11562, Egypt

    Nermin Abdel Hamid Sadik

Authors
  1. Olfat G. Shaker
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nermin Abdel Hamid Sadik
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nermin Abdel Hamid Sadik.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shaker, O.G., Sadik, N.A.H. Vaspin gene in rat adipose tissue: relation to obesity-induced insulin resistance. Mol Cell Biochem 373, 229–239 (2013). https://doi.org/10.1007/s11010-012-1494-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-012-1494-5

Keywords

Search

Navigation