title: The polygenetically inherited metabolic syndrome of male WOKW rats is associated with enhanced autophagy in adipose tissue.
abstract: BACKGROUND
  Recent studies revealed that autophagy is up-regulated in obese individuals, as evidenced by increased expression of autophagy related genes. As argued elsewhere, it is possible that initially insulin resistance functions as an adaptive mechanism to increase autophagy in order to protect cells against death. We have shown that Wistar Ottawa Karlsburg W (RT1(u)) rats (WOKW) develop a metabolic syndrome with insulin resistance in adipose tissue, closely resembling the human disease. Therefore, the aim of this study was to characterize the autophagy phenotype in WOKW rats to clarify the interrelation between insulin resistance and autophagy in adipose tissue.
  
  
  METHODS
  Subcutaneous and epidydimal adipose tissue samples of 5-months-old WOKW and healthy LEW.1 W male rats were investigated and protein levels (Western blot and immunhistochemistry) of key autophagy genes, including Atg5, Atg7, LC3-II/LC3-I and apoptosis marker cleaved caspase-3 were analyzed.
  
  
  RESULTS
  WOKW rats displayed a significant increase of autophagy related proteins (Atg5, Atg7) in adipose tissue compared with LEW.1 W. This increase was predominantly found in epididymal adipose tissue. Furthermore, the LC3-II/LC3-I ratio as a marker of autophagosomes was significantly up-regulated in subcutaneous adipose tissue of WOKW rats. Cleaved caspase-3 was just slightly detectable in visceral adipose tissue and not detected in subcutaneous fat.
  
  
  CONCLUSIONS
  Insulin resistance in adipose tissue of obese WOKW rats is associated with up-regulation of differing autophagy markers in visceral and subcutaneous fat depots. This fact not only qualifies the WOKW rat for further detailed analysis of genetic determinants of metabolic syndrome but also highlights its suitability for autophagy research.
authors.affiliation: Department of Medicine, Endocrinology and Diabetes, University Leipzig, Leipzig, Germany.
authors.forename: Joanna
authors.initials: J
authors.lastname: Kosacka
authors.affiliation: IFB AdiposityDiseases, Junior Research Group 2 "Animal models of obesity", University Leipzig, Leipzig, Germany.
authors.forename: Karoline
authors.initials: K
authors.lastname: Koch
authors.affiliation: Institute of Anatomy, University Leipzig, Leipzig, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Gericke
authors.affiliation: Institute of Anatomy, University Leipzig, Leipzig, Germany.
authors.forename: Marcin
authors.initials: M
authors.lastname: Nowicki
authors.affiliation: Department of Medicine, Endocrinology and Diabetes, University Leipzig, Leipzig, Germany.
authors.forename: John T
authors.initials: JT
authors.lastname: Heiker
authors.affiliation: Department of Laboratory Animal Science, University of Greifswald, Greifswald, Germany.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Klöting
authors.affiliation: Department of Medicine, Endocrinology and Diabetes, University Leipzig, Leipzig, Germany.|IFB AdiposityDiseases, University Leipzig, Leipzig, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Stumvoll
authors.affiliation: Department of Medicine, Endocrinology and Diabetes, University Leipzig, Leipzig, Germany.|IFB AdiposityDiseases, University Leipzig, Leipzig, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Blüher
authors.affiliation: IFB AdiposityDiseases, Junior Research Group 2 "Animal models of obesity", University Leipzig, Leipzig, Germany.
authors.forename: Nora
authors.initials: N
authors.lastname: Klöting
keywords: Adipose tissue; Atg5; Atg7; Autophagy; Insulin resistance; WOKW