Abstract
Lipid accumulation is the hallmark of Non-alcoholic Fatty Liver Disease (NAFLD) and has been suggested to play a role in promoting fatty liver inflammation. Previous findings indicate that during oxidative stress conditions excess cholesterol autoxidizes to oxysterols. To date, the role of oxysterols and their potential interaction with fatty acids accumulation in NASH pathogenesis remains little investigated.We used the nutritional model of high fatty acids (HFA), high cholesterol (HCh) or high fat and high cholesterol (HFA+FCh) diets and explored by a lipidomic approach, the blood and liver distribution of fatty acids and oxysterols in response to dietary manipulation. We observed that HFA or HCh diets induced fatty liver without inflammation, which was otherwise observed only after supplementation of HFA+HCh. Very interestingly, the combination model was associated with a specific oxysterol fingerprint.The present work provides a complete analysis of the change in lipids and oxysterols profile induced by different lipid dietary model and their association with histological alteration of the liver. This study allows the generation of interesting hypotheses on the role of interaction of lipid and cholesterol metabolites in the liver injury during NAFLD development and progression. Moreover, the changes in the concentration and quality of oxysterols induced by a combination diet suggest a novel potential pathogenic mechanism in the progression from simple steatosis to steatohepatitis.
Highlights
Serum cholesterol and LDL-cholesterol were higher in high cholesterol (HCh) and high FA (HFA) þHCh groups, and TG was higher in HFA group compared to CTRL
Concerning cholesterol and TG levels in the liver, both lipids accumulated in the liver of HFA and HFA þ HCh groups, and cholesterol but not TG accumulated in the liver of HCh group (Table 4)
Nonalcoholic fatty liver disease (NAFLD) is characterized by altered lipid homeostasis, but there is little data on the potential interaction of various lipid classes. i.e. fatty acids and cholesterol metabolism, during NAFLD development and progression
Summary
Nonalcoholic fatty liver disease (NAFLD), the most common liver pathology in the Western world [1], covers diverse clinical conditions ranging from benign steatosis (NAFL), steatohepatitis (NASH) – the most progressive form of the disease [2] – through liver cirrhosis. Accumulation of lipids in hepatocytes, the hallmark of NAFLD, is not necessarily dangerous because liver injury is caused by the quality rather than quantity of accumulated lipids.
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