Obese state leads to elevated levels of TGF-beta and COX isoforms in platelets of Zucker rats.
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-beta 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-beta1/-beta2 and COX-1/-2 proteins in platelets were analyzed by Western blot. The platelets of the Ob rats had significantly higher levels of TGF-beta1, 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-beta2 among any of the groups. These results demonstrate that cytokines and candidates playing a role in the pathogenesis of chronic diseases, such as TGF-beta1 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.
Department of Biology, University of Waterloo, Waterloo, Ontario, Canada.
Jayadev
J
Raju
Gagan
G
Bajaj
Jennifer
J
Chrusch
Ranjana P
RP
Bird
D000818:Animals; D001792:Blood Platelets / Q000201:enzymology / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000097:blood; D051545:Cyclooxygenase 1 / Q000097:blood*; D051546:Cyclooxygenase 2 / Q000097:blood*; D050528:Diet, Carbohydrate-Restricted; D002149:Energy Intake; D005260:Female; D007527:Isoenzymes / Q000097:blood; D008565:Membrane Proteins / Q000097:blood*; D009765:Obesity / Q000097:blood*; D011230:Precancerous Conditions / Q000097:blood; D051381:Rats; D011924:Rats, Zucker; D016212:Transforming Growth Factor beta / Q000097:blood*; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2
D007527:Isoenzymes; D008565:Membrane Proteins; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496513:Ptgs1 protein, rat; C489691:Ptgs2 protein, rat