Abstract
Nonalcoholic fatty liver disease (NAFLD) is a serious health problem in developed countries. We documented the effects of feeding with a NAFLD-inducing, methionine- and choline-deficient (MCD) diet, for 1–4 weeks on rat liver oxidative stress, with respect to a control diet. Glycogen, neutral lipids, ROS, peroxidated proteins, and SOD2 were investigated using histochemical procedures; ATP, GSH, and TBARS concentrations were investigated by biochemical dosages, and SOD2 expression was investigated by Western Blotting. In the 4-week-diet period, glycogen stores decreased whereas lipid droplets, ROS, and peroxidated proteins expression (especially around lipid droplets of hepatocytes) increased. SOD2 immunostaining decreased in poorly steatotic hepatocytes but increased in the thin cytoplasm of macrosteatotic cells; a trend towards a quantitative decrease of SOD expression in homogenates occurred after 3 weeks. ATP and GSH values were significantly lower for rats fed with the MCD diet with respect to the controls. An increase of TBARS in the last period of the diet is in keeping with the high ROS production and low antioxidant defense; these TBARS may promote protein peroxidation around lipid droplets. Since these proteins play key roles in lipid mobilization, storage, and metabolism, this last information appears significant, as it points towards a previously misconsidered target of NAFLD-associated oxidative stress that might be responsible for lipid dysfunction.
Highlights
Nonalcoholic fatty liver disease (NAFLD), the most recurrent liver disorder in Western countries, is commonly associated with obesity and progression of metabolic syndrome [1,2,3,4,5,6]
NAFLD comprehends a wide spectrum of disorders ranging from simple steatosis, that is, excessive accumulation of triglycerides in the liver exceeding 5% of total organ mass, to nonalcoholic steatohepatitis (NASH), characterized by progressive inflammation associated with oxidative stress and apoptosis, often progressing to fibrosis, cirrhosis, and even hepatocellular carcinoma
The purpose of the present work was to document, mainly with histochemical procedures, the progression of oxidative stress in the liver of rats induced by a methionine- and choline-deficient (MCD) diet lasting for 1 to 4 weeks, taking as reference the liver of rats submitted to a control diet, isocaloric with MCD diet, but containing methionine and choline
Summary
Nonalcoholic fatty liver disease (NAFLD), the most recurrent liver disorder in Western countries, is commonly associated with obesity and progression of metabolic syndrome [1,2,3,4,5,6]. NAFLD comprehends a wide spectrum of disorders ranging from simple steatosis, that is, excessive accumulation of triglycerides in the liver exceeding 5% of total organ mass, to nonalcoholic steatohepatitis (NASH), characterized by progressive inflammation associated with oxidative stress and apoptosis, often progressing to fibrosis, cirrhosis, and even hepatocellular carcinoma. For investigating the etiology and regulation of NAFLD and NASH and for testing potential therapeutic approaches, several experimental models were developed. These are based on the application of a diet, on the administration of drugs to laboratory animals, or on the exposure of hepatic cell lines to these drugs; genetically modified rodents or zebrafish have been introduced [7,8,9,10,11,12]. One of the most commonly used dietary models of NAFLD and NASH is the methionine- and choline-deficient (MCD) diet, capable of increasing both liver lipid accumulation and oxidative stress, the “two hits” requested for the pathogenesis of steatohepatitis [13]
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