The polygenetically inherited metabolic syndrome of male WOKW rats is associated with enhanced autophagy in adipose tissue
Tóm tắt
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 (RT1u) 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. 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. 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. 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.
Tài liệu tham khảo
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