The polygenetically inherited metabolic syndrome of male WOKW rats is associated with enhanced autophagy in adipose tissue

Diabetology & Metabolic Syndrome

Nora Klöting⁵  Matthias Blüher¹  Michael Stumvoll¹  Ingrid Klöting³  John T Heiker⁴  Marcin Nowicki²  Martin Gericke²  Karoline Koch⁵  Joanna Kosacka⁴ 

[1] IFB AdiposityDiseases, University Leipzig, Leipzig, Germany;Institute of Anatomy, University Leipzig, Leipzig, Germany;Department of Laboratory Animal Science, University of Greifswald, Greifswald, Germany;Department of Medicine, Endocrinology and Diabetes, University Leipzig, Leipzig, Germany;IFB AdiposityDiseases, Junior Research Group 2 “Animal models of obesity”, University Leipzig, Leipzig, Germany

关键词: Atg7;    Atg5;    Adipose tissue;    Insulin resistance;    WOKW;    Autophagy;   

Others  :  813940
DOI  :  10.1186/1758-5996-5-23

 received in 2013-03-27, accepted in 2013-05-08,  发布年份 2013

【 摘 要 】

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.

Conclusion

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.

【 授权许可】

   
2013 Kosacka et al.; licensee BioMed Central Ltd.

【 图 表 】

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