Up-regulated autophagy: as a protective factor in adipose tissue of WOKW rats with metabolic syndrome

作者：Kosacka J^*; Nowicki M; Paeschke S; Baum P; Blueher M; Kloeting N

来源：Diabetology & Metabolic Syndrome, 2018, 10(1): 13.

DOI：10.1186/s13098-018-0317-6

• Autophagy
• Adipose tissue
• LY294002 inhibitor
• Metabolic syndrome
• WOKW rats

Background: Wistar Ottawa Karlsburg W (RT1u) rats (WOKW) are a model of the metabolic syndrome (MetS). Adipose tissue (AT) and peripheral nerves of WOKW rats exhibit up-regulated autophagy and inflammation corresponding with decreased apoptosis rate. The aim of this study was to characterize AT in WOKW rats in relation to autophagic activity.
Methods: mRNA and protein expression of adiponectin, pro-inflammatory and pro-apoptotic markers including MCP1, TNFa, cleaved caspase-3 and RNF157, a new candidate gene regulated through autophagy, were analyzed in adipocytes isolated from visceral and subcutaneous AT of 5-month old WOKW rats with MetS and LEW. 1W controls in response to pharmacological inhibition of autophagy. Immunohistochemistry was performed to detect adiponectin and RNF157 protein in cultured adipocytes.
Results: Inhibition of autophagy by LY294002 was associated with a fourfold up-regulation of adiponectin expression and a decrease of RNF157 protein and pro-inflammatory markers-MCP-1 and TNF alpha predominantly in visceral adipocytes of obese WOKW rats compared to LEW. 1W rats. Moreover, inhibition of autophagic activity correlates with an activation of cleaved caspase-3 apoptotic signaling pathway.
Conclusions: Up-regulated autophagy in obese WOKW rats contributes to the regulation of visceral AT function and involves an altered balance between pro- inflammatory and protective adipokine expression. Our data suggest that activation of AT autophagy protects against adipocyte apoptosis at least under conditions of obesity related MetS in WOKW rats.

• 出版日期2018-3-2