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

J Kosacka,S Paeschke,M Nowicki,M Blüher,N Klöting,P Baum

doi:10.1186/s13098-018-0317-6

J Kosacka, S Paeschke + Show 4 more

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https://doi.org/10.1186/s13098-018-0317-6

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Abstract

BackgroundWistar 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.MethodsmRNA and protein expression of adiponectin, pro-inflammatory and pro-apoptotic markers including MCP1, TNFα, 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.ResultsInhibition 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 TNFα 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.ConclusionsUp-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.

Highlights

Wistar Ottawa Karlsburg W (RT1u) rats (WOKW) are a model of the metabolic syndrome (MetS)
WOKW rats have a significantly higher body weight as well as fasting serum insulin concentrations compared to healthy LEW.1W rats
Inhibition of autophagy in visceral and subcutaneous adipocyte cell cultures of WOKW and LEW.1W rats We have previously shown the strikingly up-regulated autophagy in adipose depots of obese WOKW rats with metabolic syndrome in correlation with inhibition of caspase-3 apoptotic signal pathway [15]

Summary

Introduction

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. The metabolic syndrome (MetS) characterized by obesity, hypertension, hyperinsulinemia, dyslipidemia and impaired glucose metabolism represents a risk factor for cardiovascular diseases and type 2 diabetes. Inflammation of adipose tissue (AT)—a symptom of AT dysfunction both in humans and model organisms which develops with weight gain and diabetes—is associated with AT autophagic activity [7,8,9]. Autophagy has been shown to prevent or induce inflammatory responses and to regulate of cytokine production in AT of obesity in humans and animal models Activated autophagy has been generally considered as a cell-protection mechanism, which promotes cell survival; the excessive activation of autophagy may lead to autophagic cell death [11].

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