Abstract

BackgroundGeneral overnutrition is one of the key factors involved in the development of nonalcoholic fatty liver disease (NAFLD) as the most common liver disease occur by two steps of liver injury ranges from steatosis to nonalcoholic steatohepatitis (NASH). Here the effect of fructose, fat-rich and western diet (WD) feeding was studied along with aggravative effect of cigarette smoking on liver status in mice.MethodsSixty-four male NMRI mice were included in this study and assigned into 4 groups that fed standard, fructose-rich, high fat-, and western-diet for 8 weeks and then each group divided in two smoker and nonsmoker subgroups according to smoke exposing in the last 4 weeks of feeding time (n = 8). Histopathological studies, serum biochemical analyses and hepatic TNF-α level were evaluated in mice to compare alone or combination effects of dietary regimen and cigarette smoking.ResultsSerum liver enzymes and lipid profile levels in WD fed mice were significantly higher than in other studied diets. Exposing to cigarette smoke led to more elevation of serum biochemical parameters that was also accompanied by a significant increase in hepatic damage shown as more severe fat accumulation, hepatocyte ballooning and inflammation infiltrate. Elevated TNF-α level confirmed incidence of liver injury.ConclusionThe finding of this study demonstrated that a combination of cigarette smoke exposure and WD (rich in fat, fructose, and cholesterol) could induce a more reliable mouse model of NASH.

Highlights

  • General overnutrition is one of the key factors involved in the development of nonalcoholic fatty liver disease (NAFLD) as the most common liver disease occur by two steps of liver injury ranges from steatosis to nonalcoholic steatohepatitis (NASH)

  • Over the last several decades, there is increasing concern about the rising daily exposure to cigarette smoke along with hyper-calorie intake on human health [1,2,3]. This global change in dietary habits is likely to contribute to the generation of intrahepatic lipid subsequently, renders the hepatocytes susceptible to a variety of damages that increased the probability of disease progression to more severe conditions, including nonalcoholic steatohepatitis (NASH) [1, 4, 5]

  • We outlined a mouse model to determine the effects of caloric excess and damaging role of cigarette smoking to induce model of NAFLD that progress to NASH and attempted to compare three different dietary patterns provided as diet enriched with fructose, fat or western diet

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Summary

Introduction

General overnutrition is one of the key factors involved in the development of nonalcoholic fatty liver disease (NAFLD) as the most common liver disease occur by two steps of liver injury ranges from steatosis to nonalcoholic steatohepatitis (NASH). Over the last several decades, there is increasing concern about the rising daily exposure to cigarette smoke along with hyper-calorie intake on human health [1,2,3]. This global change in dietary habits is likely to contribute to the generation of intrahepatic lipid subsequently, renders the hepatocytes susceptible to a variety of damages that increased the probability of disease progression to more severe conditions, including nonalcoholic steatohepatitis (NASH) [1, 4, 5]. According to the current pathogenic factors especially dietary factors, that have been lead to disease development and progression and matches modern lifestyle, a reliable disease model should be induced by diet and not by administration of chemical toxins and/or genetic manipulation [7, 9]

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