Fatty Liver ; metabolism ; pathology ; Humans ; Inflammation ; Lipidoses ; metabolism ; pathology ; Non-alcoholic Fatty Liver Disease

Animals ; Endoplasmic Reticulum ; metabolism ; Fatty Liver ; metabolism ; pathology ; Humans ; Mitochondria ; metabolism ; Non-alcoholic Fatty Liver Disease

Liver plays a central role in the biogenesis of major metabolites including glucose, fatty acids, and cholesterol. Increased incidence of obesity in the modern society promotes insulin resistance in the peripheral tissues in humans, and could cause severe metabolic disorders by inducing accumulation of lipid in the liver, resulting in the progression of non-alcoholic fatty liver disease (NAFLD). NAFLD, which is characterized by increased fat depots in the liver, could precede more severe diseases such as non-alcoholic steatohepatitis (NASH), cirrhosis, and in some cases hepatocellular carcinoma. Accumulation of lipid in the liver can be traced by increased uptake of free fatty acids into the liver, impaired fatty acid beta oxidation, or the increased incidence of de novo lipogenesis. In this review, I would like to focus on the roles of individual pathways that contribute to the hepatic steatosis as a precursor for the NAFLD.
Acetyl Coenzyme A/metabolism ; Fatty Acids/metabolism ; Fatty Liver/*metabolism/pathology ; Humans ; Lipogenesis ; Mitochondria/metabolism ; Triglycerides/metabolism

Fatty Liver ; metabolism ; pathology ; Humans ; Inflammation ; Non-alcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is a type of metabolic stress liver injury that is closely associated with insulin resistance and genetic susceptibility. The continuum of liver injury in NAFLD can range from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) and even lead to cirrhosis and liver cancer. The pathogenesis of NAFLD is complicated. Pro-inflammatory cytokines, lipotoxicity, and gut bacterial metabolites play a key role in activating liver-resident macrophages (Kupffer cells, KCs) and recruiting circulating monocyte-derived macrophages (MoDMacs) to deposit fat in the liver. With the application of single-cell RNA-sequencing, significant heterogeneity in hepatic macrophages has been revealed, suggesting that KCs and MoDMacs located in the liver exert distinct functions in regulating liver inflammation and NASH progression. This study focuses on the role of macrophage heterogeneity in the development and occurrence of NAFLD and NASH, in view of the fact that innate immunity plays a key role in the development of NAFLD.
Humans ; Non-alcoholic Fatty Liver Disease/pathology* ; Liver/pathology* ; Macrophages/metabolism* ; Liver Cirrhosis/complications* ; Disease Progression

BACKGROUND/AIMS: Nonalcoholic steatohepatitis (NASH) is chronic liver disease that can potentially progress to end stage liver disease. Oxidative stress to the vulnerable fatty liver has been reported as a key mechanism in development of NASH. Several antioxidant pathways have been identified, but reports that involved quantitative analysis of each antioxidant systems are rare, and these reports have shown various results. So, we investigated antioxidant status and the degree of oxidative stress by measuring several antioxidant enzymes, the total antioxidant status (TAS), and the metabolites of superoxide in NASH patients. METHODS: Nineteen NASH patients who were confirmed by liver biopsy and fifteen controls were involved in this study. The levels of body mass index (BMI), AST, ALT, superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase, TAS, hydrogen peroxide (H2O2), and malondialdehyde (MDA) were compared between both groups. The relationship between the histologic severity and the levels of each antioxidants were analyzed in the NASH group. RESULTS: The activities of SOD and catalase were lower in the NASH group. The concentrations of TAS and H2O2 were higher in NASH group. The level of GPx and MDA showed no significant differences between both groups. There were no significant relationships between the above variables and the pathological severity. CONCLUSIONS: The disturbed metabolism of superoxide due to the decreased activities of SOD and catalase seem to be important in the pathogenesis of NASH. Further investigations about the nonenzymatic secondary antioxidant mechanism are necessary because the TAS was higher for the NASH group. The lack of difference between both groups for the concentration of MDA indicates that mechanisms other than lipid peroxidation also may be important in the pathogenesis of NASH.
Adult ; Antioxidants/*metabolism ; English Abstract ; Fatty Liver/*metabolism/pathology ; Female ; Humans ; Liver/pathology ; Male ; Oxidative Stress

OBJECTIVETo investigate the changes of osteopontin (OPN) in the liver tissues during nonalcoholic fatty liver fibrosis in rats and to explore the effect of OPN in the development of nonalcoholic fatty liver fibrosis.

METHODSFifty-six male Wistar rats were randomly divided into a control group (8 rats) and a high-fat diet group. The high-fat diet group was divided into 6 subgroups (8 rats in each subgroup) with high-fat feedings for 4, 8, 12, 16, 20 or 24 weeks. Conventional histochemical, HE, Masson-trichrome and immunohistochemical staining for alpha-smooth muscle actin (a-SMA) were performed with the liver histological preparations. The expression of OPN was detected with reverse transcription and polymerase chain reactions and Western blot.

RESULTSLevels of OPN in liver tissues in rat nonalcoholic fatty liver fibrosis induced by high-fat diet were significantly increased over those in the control group (F=7.15, P less than 0.01). OPN expressions were closely correlated with a-SMA and nonalcoholic fatty liver fibrosis, and correlation coefficients of the two groups were 0.94 and 0.82, and both P values were less than 0.01.

CONCLUSIONExpression of OPN increases dramatically in the livers during the development of nonalcoholic fatty liver fibrosis, and OPN may play an important role in this event.

Animals ; Fatty Liver ; metabolism ; pathology ; Liver ; pathology ; Liver Cirrhosis ; metabolism ; pathology ; Male ; Osteopontin ; metabolism ; Rats ; Rats, Wistar

Adult ; Fatty Liver ; etiology ; metabolism ; pathology ; Humans ; Liver ; metabolism ; Middle Aged ; Resistin ; metabolism

Animals ; Disease Progression ; Fatty Liver ; metabolism ; pathology ; Humans ; Inflammation ; Kupffer Cells ; metabolism ; Non-alcoholic Fatty Liver Disease

Metabolic associated fatty liver disease (MAFLD) is a liver disease with hepatocyte steatosis caused by metabolic disorders, which is closely related to obesity, diabetes, metabolic dysfunction, and other factors. Its pathological process changes from simple steatosis, liver inflammation to non-alcoholic steatohepatitis (NASH), and then leads to liver fibrosis, cirrhosis, and liver cancer. At present, no specific therapeutics are available for treatment of MAFLD targeting its etiology. Celastrol is the main active component of the traditional Chinese medicine Celastrus orbiculatus Thunb. In recent years, it has been found that celastrol shows important medicinal value in regulating lipid metabolism, reducing fat and weight, and protecting liver, and then ameliorates MAFLD. This article reviews the related research progress of celastrol in the prevention and treatment of MAFLD, so as to provide a reference for the comprehensive development and utilization of celastrol.
Humans ; Non-alcoholic Fatty Liver Disease/metabolism* ; Liver/pathology* ; Pentacyclic Triterpenes/metabolism* ; Obesity