The polygenetically inherited metabolic syndrome of WOKW rats is associated with insulin resistance and altered gene expression in adipose tissue.
BACKGROUND
Wistar Ottawa Karlsburg W (RT1u) rats (WOKW) develop a complete metabolic syndrome closely resembling the human disease. The aim of this study was to characterize the phenotype of adipose tissue in WOKW rats with regard to adipocyte metabolism, insulin resistance, and gene expression and thus to define the phenotype more precisely.


METHODS
Glucose metabolism, insulin sensitivity, and gene expression of key adipocyte genes, including adiponectin, interleukin 6 (Il6), 11 beta-hydroxysteroid dehydrogenase (11beta Hsd), peroxisome proliferator-activated receptor gamma (Ppar gamma), forkhead box O1 (Foxo1), glucose transporter 4 (Glut4), CCAAT/enhancer binding protein (C/ebp alpha), and fatty acid synthase (Fasn) were characterized in adipocytes from epididymal and subcutaneous fat depots of 28-week-old male WOKW rats and Dark Agouti (DA) controls.


RESULTS
WOKW rats display decreased insulin-stimulated glucose uptake and decreased insulin sensitivity during lipogenesis and lipolysis in isolated adipocytes. The severe insulin resistance predominantly in epididymal adipose tissue of WOKW rats is associated with a 10-fold decrease in adipocyte adiponectin gene expression, decreased Ppar gamma, but increased Foxo1 gene expression compared to DA rats.


CONCLUSIONS
Insulin resistance in adipose tissue is associated with altered adipocyte gene expression in WOKW rats, additionally completing the picture of the metabolic syndrome in this animal model. This fact not only qualifies the WOKW rat for further detailed analysis of genetic determinants of metabolic syndrome but also highlights its suitability for pharmacological research.
Klöting
Nora
N
Department of Laboratory Animal Science, Medical Faculty, University of Greifswald, Karlsburg, Germany.
Blüher
Matthias
M
Klöting
Ingrid
I
D017667:Adipocytes / Q000166:cytology / Q000473:pathology / Q000502:physiology; D000273:Adipose Tissue / Q000503:physiopathology*; D000818:Animals; D001692:Biological Transport / Q000235:genetics; D002245:Carbon Dioxide / Q000378:metabolism; D017931:DNA Primers; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism*; D007333:Insulin Resistance / Q000235:genetics*; D007773:Lactates / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000096:biosynthesis
D017931:DNA Primers; D007773:Lactates; D014280:Triglycerides; D002245:Carbon Dioxide; D005947:Glucose