Reduction of oxidative stress improves insulin signaling in cardiac tissue of obese mice.

Matheus Scarpatto Rodrigues,Bruno Luiz Da Silva Pieri,Karine Damian Luiz,Paulo Cesar Lock Silveira,Rubya Pereira Zaccaron,Vitor Hugo Comin,Ligia Milanez Venturini,Gustavo De Bem Silveira

doi:10.31744/einstein_journal/2020ao5022

Matheus Scarpatto Rodrigues, Bruno Luiz Da Silva Pieri + Show 6 more

Open Access

https://doi.org/10.31744/einstein_journal/2020ao5022

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Abstract

ABSTRACTObjectiveTo evaluate the effects of oxidative stress on insulin signaling in cardiac tissue of obese mice.MethodsThirty Swiss mice were equally divided (n=10) into three groups: Control Group, Obese Group, and Obese Group Treated with N-acetylcysteine. After obesity and insulin resistance were established, the obese mice were treated with N-acetylcysteine at a dose of 50mg/kg daily for 15 days via oral gavage.ResultsHigher blood glucose levels and nitrite and carbonyl contents, and lower protein levels of glutathione peroxidase and phosphorylated protein kinase B were observed in the obese group when compared with their respective control. On the other hand, treatment with N-acetylcysteine was effective in reducing blood glucose levels and nitrite and carbonyl contents, and significantly increased protein levels of glutathione peroxidase and phosphorylated protein kinase B compared to the Obese Group.ConclusionObesity and/or a high-lipid diet may result in oxidative stress and insulin resistance in the heart tissue of obese mice, and the use of N-acetylcysteine as a methodological and therapeutic strategy suggested there is a relation between them.

Highlights

Obesity is a worldwide and multiethnic public health problem, which affects men and women of all age groups and social classes.[1,2] Epidemiological data reinforce the prevalence of this condition in the world population
The mice were initially divided into two groups: 10 animals fed with the standard diet for rodents (Control Group) and the remaining 20 animals fed a high-fat diet, after obesity and insulin resistance were proven, were subdivided into two other experimental groups: Obese Group (n=10) and Obese Group Treated with N-acetylcysteine (n=10)
Treating the animals with the antioxidant N-acetylcysteine After obesity and insulin resistance had been induced, the animals who had previously received the highfat diet were subdivided into two groups: Group OB, obese mice who were given the high-fat diet (n=10); and Group OB + NAC, obese mice treated with NAC for 15 days (n=10)

Summary

Introduction

Obesity is a worldwide and multiethnic public health problem, which affects men and women of all age groups and social classes.[1,2] Epidemiological data reinforce the prevalence of this condition in the world population. Several strategies have been used to experimentally study obesity, especially the model of induction through a high fat diet (hyperlipid diet).(6,7) Mice that underwent such diet presented significant cardiac problems, such as myocardial fibrosis, cardiomyocyte hypertrophy, and a decreased contractile capacity of the heart.[8] Obese mice presented deficits in glucose uptake and a reduction of insulin sensitivity in the myocardium.[9]. N-acetylcysteine is a compound often employed in clinical practice as a mucolytic agent to treat paracetamol overdoses and prevent free radical generation by toxic substances.[13] Its antioxidant activity is related mainly to the reduction of the extracellular amino acid cystine into the intracellular amino acid cysteine, and to the donation of thiol groups to reduced glutathione.[14] NAC can promote the direct neutralization of ROS as the radical hydroxyl and hypochlorous acid, preventing the occurrence of oxidative stress and its possible consequences over insulin resistance.[15]

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