4.Macrophage heterogeneity role in NAFLD and NASH disease progression.
Tao YANG ; Xiao WANG ; Long Feng JIANG ; Jun LI
Chinese Journal of Hepatology 2023;31(7):770-775
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
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Non-alcoholic Fatty Liver Disease/pathology*
;
Liver/pathology*
;
Macrophages/metabolism*
;
Liver Cirrhosis/complications*
;
Disease Progression
5.Nonalcoholic fatty liver disease and bilirubin: correlation, mechanism, and therapeutic perspectives.
Nian Chen LIU ; Zhong Ping DUAN ; Su Jun ZHENG
Chinese Journal of Hepatology 2023;31(1):101-104
Non-alcoholic fatty liver disease (NAFLD) is a metabolic-related disorder induced by multiple factors and mainly characterized by excessive fat buildup in hepatocytes. With the consumption of a Western-style diet and obesity prevalence in recent years, the incidence of NAFLD has gradually increased, becoming an increasingly serious public health problem. Bilirubin is a heme metabolite and a potent antioxidant. Studies have demonstrated that bilirubin levels have an inverse correlation with the incidence rate of NAFLD; however, which form of bilirubin plays the main protective role is still controversial. It is considered that the main protective mechanisms for NAFLD are bilirubin antioxidant properties, insulin resistance reduction, and mitochondrial function. This article summarizes the correlation, protective mechanism, and possible clinical application of NAFLD and bilirubin.
Humans
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Non-alcoholic Fatty Liver Disease/metabolism*
;
Bilirubin
;
Antioxidants
;
Obesity/complications*
;
Hepatocytes/metabolism*
;
Liver/metabolism*
6.Research progress of celastrol on the prevention and treatment of metabolic associated fatty liver disease.
Yun-Chao LIU ; Ying ZHANG ; Shu-Cun QIN ; Jun-Li XUE
Acta Physiologica Sinica 2023;75(5):682-690
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
8.The Immune Landscape in Nonalcoholic Steatohepatitis.
Sowmya NARAYANAN ; Fionna A SURETTE ; Young S HAHN
Immune Network 2016;16(3):147-158
The liver lies at the intersection of multiple metabolic pathways and consequently plays a central role in lipid metabolism. Pathological disturbances in hepatic lipid metabolism are characteristic of chronic metabolic diseases, such as obesity-mediated insulin resistance, which can result in nonalcoholic fatty liver disease (NAFLD). Tissue damage induced in NAFLD activates and recruits liver-resident and non-resident immune cells, resulting in nonalcoholic steatohepatitis (NASH). Importantly, NASH is associated with an increased risk of significant clinical sequelae such as cirrhosis, cardiovascular diseases, and malignancies. In this review, we describe the immunopathogenesis of NASH by defining the known functions of immune cells in the progression and resolution of disease.
Cardiovascular Diseases
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Fatty Liver
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Fibrosis
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Insulin Resistance
;
Lipid Metabolism
;
Liver
;
Metabolic Diseases
;
Metabolic Networks and Pathways
;
Non-alcoholic Fatty Liver Disease*
9.PIK3R3 regulates PPARα expression to stimulate fatty acid β-oxidation and decrease hepatosteatosis
Xi YANG ; Yinjia FU ; Fuqing HU ; Xuelai LUO ; Junbo HU ; Guihua WANG
Experimental & Molecular Medicine 2018;50(1):e431-
Phosphatidylinositol 3-kinase (PI3K) signaling plays an important role in the regulation of cellular lipid metabolism and non-alcoholic fatty liver disease (NAFLD). However, little is known about the role of the regulatory subunits of PI3K in lipid metabolism and NAFLD. In this study, we characterized the functional role of PIK3R3 in fasting-induced hepatic lipid metabolism. In this study, we showed that the overexpression of PIK3R3 promoted hepatic fatty acid oxidation via PIK3R3-induced expression of PPARα, thus improving the fatty liver phenotype in high-fat diet (HFD)-induced mice. By contrast, hepatic PIK3R3 knockout in normal mice led to increased hepatic TG levels. Our study also showed that PIK3R3-induced expression of PPARα was dependent on HNF4α. The novel PIK3R3-HNF4α-PPARα signaling axis plays a significant role in hepatic lipid metabolism. As the activation of PIK3R3 decreased hepatosteatosis, PIK3R3 can be considered a promising novel target for developing NAFLD and metabolic syndrome therapies.
Animals
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Diet, High-Fat
;
Fatty Liver
;
Lipid Metabolism
;
Mice
;
Non-alcoholic Fatty Liver Disease
;
Phenotype
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Phosphatidylinositol 3-Kinase