A Novel Wistar Rat Model of Obesity-Related Nonalcoholic Fatty Liver Disease Induced by Sucrose-Rich Diet.

Maria Luíza R P Lima,Virginia H R Leite,Cândido C Coimbra,Claudia A Couto,Carolina R Gioda,Teresa Cristina A Ferrari,Laura H R Leite,Fabíola O P Leme

doi:10.1155/2016/9127076

Abstract

The pathogenesis of nonalcoholic fatty liver disease (NAFLD) is not fully understood, and experimental models are an alternative to study this issue. We investigated the effects of a simple carbohydrate-rich diet on the development of obesity-related NAFLD and the impact of physical training on the metabolic abnormalities associated with this disorder. Sixty Wistar rats were randomly separated into experimental and control groups, which were fed with sucrose-enriched (18% simple carbohydrates) and standard diet, respectively. At the end of each experimental period (5, 10, 20, and 30 weeks), 6 animals from each group were sacrificed for blood tests and liver histology and immunohistochemistry. From weeks 25 to 30, 6 animals from each group underwent physical training. The experimental group animals developed obesity and NAFLD, characterized histopathologically by steatosis and hepatocellular ballooning, clinically by increased thoracic circumference and body mass index associated with hyperleptinemia, and metabolically by hyperglycemia, hyperinsulinemia, hypertriglyceridemia, increased levels of very low-density lipoprotein- (VLDL-) cholesterol, depletion of the antioxidants liver enzymes superoxide dismutase and catalase, and increased hepatic levels of malondialdehyde, an oxidative stress marker. Rats that underwent physical training showed increased high-density lipoprotein- (HDL-) cholesterol levels. In conclusion, a sucrose-rich diet induced obesity, insulin resistance, oxidative stress, and NAFLD in rats.

Highlights

Over the last decades, obesity has become a global epidemic and an important public health problem in many countries [1]
Excessive deposition of fat in adipocytes and muscles determines insulin resistance with subsequent accumulation of fat in the liver [9], which, in turn, increases the rate of mitochondrial beta-oxidation of fatty acids and ketogenesis that can promote lipid peroxidation and accumulation of reactive oxygen species (ROS) in the hepatocytes [10, 11]. These compounds generate a variety of cellular stimulations with subsequent inflammatory response, which has been recognized as the causal factor of NASH/fibrosis [12, 13]
This study demonstrates that a diet with high amount of simple carbohydrates, which resembles the current human dietary pattern, was able to induce obesity-related nonalcoholic fatty liver disease (NAFLD), here characterized histologically by hepatic steatosis and hepatocyte ballooning, clinically by increased thoracic circumference (TC) and Body mass index (BMI) associated with hyperleptinemia, and metabolically by hyperglycemia, hyperinsulinemia, hypertriglyceridemia, increased serum levels of VLDL-cholesterol, depletion of antioxidants liver enzymes, and increased levels of MDA, an oxidative stress marker

Summary

Introduction

Obesity has become a global epidemic and an important public health problem in many countries [1]. Excessive deposition of fat in adipocytes and muscles determines insulin resistance with subsequent accumulation of fat in the liver [9], which, in turn, increases the rate of mitochondrial beta-oxidation of fatty acids and ketogenesis that can promote lipid peroxidation and accumulation of reactive oxygen species (ROS) in the hepatocytes [10, 11]. These compounds generate a variety of cellular stimulations with subsequent inflammatory response, which has been recognized as the causal factor of NASH/fibrosis (second causative step) [12, 13]

Methods

Results

Conclusion