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Obese state leads to elevated levels of TGF-β and COX isoforms in platelets of Zucker rats

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Abstract

Platelets are rich sources of growth factors and enzymes that are implicated in a number of diseases including obesity, atherosclerosis, heart disease, syndrome X, liver and kidney diseases and certain types of cancers. In this research we investigated, if platelets in Zucker obese rats differ from their lean counterparts with respect to the levels of TGF-β and COX isoforms, implicated in the pathogenesis of chronic diseases. In addition, we investigated if energy intake of the animals affects the platelet physiology. Platelets were isolated from obese and lean rats bearing preneoplastic lesions in their colon. Prior to platelet isolation these rats were fed either ad libitum (Ob or Ln) or energy restricted (Ob-ER or Ln-ER) diets for 8 weeks (n = 8/group). The levels of TGF-β1/-β2 and COX-1/-2 proteins in platelets were analyzed by Western blot. The platelets of the Ob rats had significantly higher levels of TGF-β1, COX-1/-2 (p < 0.001) than did the platelets of the Ln rats and were not affected by moderate energy restriction. There were no significant differences in the protein expression of platelet TGF-β2 among any of the groups. These results demonstrate that cytokines and candidates playing a role in the pathogenesis of chronic diseases, such as TGF-β1 and COX-1/-2, are over-expressed in platelets of Zucker obese rats by comparison to their lean counterparts. These findings also demonstrate that the genotype of the animals exerts a significant effect on the biochemical composition of the platelets and could contribute to the pathogenesis of colon cancer and other metabolic abnormalities associated with obesity.

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References

  • Kushner RF: Medical management of obesity, Semin Gastrointest Dis 13(3): 123–132, 2002

    Google Scholar 

  • Valettas N, Herrmann HC: The role of platelets and platelet inhibition in acute myocardial infarction. Coronary Art Dis 14: 357–363, 2003

    Article  Google Scholar 

  • Huo Y, Ley KF: Role of platelets in the development of atherosclerosis. Trends Cardiovasc Med 14: 18–22, 2004

    Article  PubMed  CAS  Google Scholar 

  • Danese S, Motte Cd Cde L, Fiocchi C: Platelets in inflammatory bowel disease: clinical, pathogenic, and therapeutic implications. Am J Gastroenterol 99: 938–945, 2004

    Article  PubMed  Google Scholar 

  • Sierko E, Wojtukiewicz MZ: Platelets and angiogenesis in malignancy. Semin Thromb Hemost 30: 95–108, 2004

    Article  PubMed  CAS  Google Scholar 

  • Anitua E, Andia I, Ardanza B, Nurden P, Nurden AT: Autologous platelets as a source of proteins for healing and tissue regeneration. Thromb Haemost 91: 4–15, 2004

    PubMed  CAS  Google Scholar 

  • Raju J, Bird RP: Differential modulation of transforming growth factor-βs and cyclooxygenases in the platelet lysates of male F344 rats by dietary lipids and piroxicam. Mol Cell Biochem 231: 139–146, 2002

    Article  PubMed  CAS  Google Scholar 

  • Adam JM, Raju J, Khalil N, Bird RP: Evidence for the involvement of dietary lipids on the modulation of transforming growth factor-beta1 in the platelets of male rats. Mol Cell Biochem 211: 145–152, 2000

    Article  PubMed  CAS  Google Scholar 

  • Raju J, Bird RP: Energy restriction reduces the number of advanced aberrant crypt foci and attenuates the expression of colonic TGF-β and COX isoforms in Zucker obese (fa/fa) rats. Cancer Res 63: 6595–6601, 2003

    PubMed  CAS  Google Scholar 

  • Murphy TK, Calle EE, Rodriguez C, Kahn HS, Thun MJ: Body mass index and colon cancer mortality in a large prospective study. Am J Epidemiol 152: 847–854, 2000

    Article  PubMed  CAS  Google Scholar 

  • Ford ES: Body mass index and colon cancer in a national sample of adult US men and women. Am J Epidemiol 150: 390–398, 1999

    PubMed  CAS  Google Scholar 

  • Weber RV, Stein DE, Scholes J, Kral JG: Obesity potentiates AOM-induced colon cancer. Dig Dis Sci 45(5): 890–895, 2000

    Article  PubMed  CAS  Google Scholar 

  • Fain JN, Ballou LR, Bahouth SW: Obesity is induced in mice heterozygous for cyclooxygenase-2. Prostaglandins Other Lipid Mediat 65: 199–209, 2001

    Article  PubMed  CAS  Google Scholar 

  • Samad F, Yamamoto K, Pandey M, Loskutoff DJ: Elevated expression of transforming growth factor-beta in adipose tissue from obese mice. Mol Med 3: 37–48, 1997

    PubMed  CAS  Google Scholar 

  • American Institute of Nutrition, Report of the ad hoc committee on standards for nutrition studies. J Nutr 123: 1939–1951, 1993

    Google Scholar 

  • Lasko CM, Bird RP: Modulation of aberrant crypt foci by dietary fat and caloric restriction: the effects of delayed intervention. Cancer Epidemiol Biomarkers Prev 4: 49–55, 1995

    PubMed  CAS  Google Scholar 

  • Heemskerk JW, Feijge MA, Kalfusz R, Hornstra G: Influence of dietary fatty acids on membrane fluidity and activation of rat platelets. Biochim Biophys Acta 1004: 252–260, 1989

    PubMed  CAS  Google Scholar 

  • McCaleb ML, Sredy J: Metabolic abnormalities of the hyperglycemic obese Zucker rat. Metabolism 41: 522–525, 1992

    Article  PubMed  CAS  Google Scholar 

  • Bray GA: The Zucker-fatty rat: a review, Fed Proc 36(2): 148–153, 1977

    Google Scholar 

  • Liu RH, Mizuta M, Kurose T, Matsukura S: Early events involved in the development of insulin resistance in Zucker fatty rat. Int J Obes Relat Metab Disord. 26(3): 318–326, 2002

    Article  Google Scholar 

  • Nash GF, Turner LF, Scully MF, Kakkar AK: Platelets and cancer. Lancet Oncol 3: 425–430, 2002

    Article  PubMed  CAS  Google Scholar 

  • Verheul HM, Pinedo HM: The importance of platelet counts and their contents in cancer. Clin Cancer Res 9: 3219–3221, 2003

    PubMed  CAS  Google Scholar 

  • Verheul HM, Hoekman K, Luykx-de Bakker S, Eekman CA, Folman CC, Broxterman HJ, Pinedo HM: Platelet: transporter of vascular endothelial growth factor. Clin Cancer Res 3: 2187–2190, 1997

    PubMed  CAS  Google Scholar 

  • Salven P, Orpana A, Joensuu H: Leukocytes and platelets of patients with cancer contain high levels of vascular endothelial growth factor. Clin Cancer Res 5: 487–491, 1999

    PubMed  CAS  Google Scholar 

  • Belloc C, Lu H, Soria C, Fridman R, Legrand Y, Menashi S: The effect of platelets on invasiveness and protease production of human mammary tumor cells. Int J Cancer 60: 413–417, 1995

    Article  PubMed  CAS  Google Scholar 

  • Kim YJ, Borsig L, Han HL, Varki NM, Varki A: Distinct selectin ligands on colon carcinoma mucins can mediate pathological interactions among platelets, leukocytes, and endothelium. Am J Pathol 155: 461–472, 1999

    Google Scholar 

  • Hanahan D, Folkman J: Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86: 353–364, 1996

    Article  PubMed  CAS  Google Scholar 

  • Raju J, McCarthy B, Bird RP: Steady state levels of transforming growth factor-β1 and -β2 mRNA and protein expression are elevated in colonic tumors in vivo irrespective of dietary lipids intervention. Int J Cancer 100: 635–641, 2002

    Article  PubMed  CAS  Google Scholar 

  • Bird RP, Good CK: The significance of aberrant crypt foci in understanding the pathogenesis of colon cancer. Toxicol Lett 112–113: 395–402, 2000

    Article  Google Scholar 

  • Govinden R, Bhoola KD: Genealogy, expression, and cellular function of transforming growth factor-beta. Pharmacol Ther 98: 257–265, 2003

    Article  PubMed  CAS  Google Scholar 

  • DuBois RN: Cyclooxygenase-2 and colorectal cancer. Prog Exp Tumor Res 37: 124–137, 2003

    Article  PubMed  CAS  Google Scholar 

  • Alessi MC, Bastelica D, Morange P, Berthet B, Leduc I, Verdier M, Geel O, Juhan-Vague I: Plasminogen activator inhibitor 1, transforming growth factor-beta1, and BMI are closely associated in human adipose tissue during morbid obesity. Diabetes 49: 1374–1380, 2000

    Article  PubMed  CAS  Google Scholar 

  • Landgraf-Leurs MM, Loy A, Christea C, Weber PC, Siess W, Herberg} LL, Landgraf R: Aggregation and thromboxane B2 formation in platelets and vascular prostacyclin production from genetically obese rats. Prostaglandins 22: 521–536, 1981

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Ranjana P. Bird.

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Raju, J., Bajaj, G., Chrusch, J. et al. Obese state leads to elevated levels of TGF-β and COX isoforms in platelets of Zucker rats. Mol Cell Biochem 284, 19–24 (2006). https://doi.org/10.1007/s11010-005-9008-3

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  • DOI: https://doi.org/10.1007/s11010-005-9008-3

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