Macrophages in Nonalcoholic Fatty Liver Disease: A Role Model of Pathogenic Immunometabolism

2017 ◽  
Vol 37 (03) ◽  
pp. 189-197 ◽  
Author(s):  
Oliver Krenkel ◽  
Frank Tacke
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Role Model ◽  
Inflammatory Responses ◽  
Macrophage Polarization ◽  
Nonalcoholic Fatty Liver ◽  
Inflammatory Stimuli ◽  
Functional Polarization

AbstractNonalcoholic fatty liver disease (NAFLD) and its progressive inflammatory form, nonalcoholic steatohepatitis (NASH), are leading causes of liver cirrhosis and hepatocellular carcinoma. Metabolism and inflammation are intimately interrelated in NAFLD/NASH, as expressed by the term immunometabolism. Hepatic macrophages mediate inflammatory responses during metabolic disorders and can stimulate or dismantle liver fibrosis. Their functional diversity is partly explained by heterogeneous macrophage subsets: tissue-resident Kupffer cells and monocyte-derived macrophages. However, macrophages themselves are altered in their functional polarization by dietary composition and metabolic or inflammatory stimuli in NAFLD. The inflammatory polarization of macrophages correlates with changes in core metabolism pathways like oxidative phosphorylation and glycolysis. The availability of nutrients, such as glucose or fatty acids or oxygen also influences macrophage polarization upon danger signal or cytokine reception. Understanding the interplay of metabolism and macrophage function in NASH may open new approaches to therapeutic targeting of these essential modifiers in metabolic liver diseases.

scholarly journals Zonarol Protected Liver from Methionine- and Choline-Deficient Diet—Induced Nonalcoholic Fatty Liver Disease in a Mouse Model

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3455
Author(s):  
Jia Han ◽  
Xin Guo ◽  
Tomoyuki Koyama ◽  
Daichi Kawai ◽  
Jing Zhang ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Inflammatory Responses ◽  
Oral Treatment ◽  
Control Group ◽  
Related Factor ◽  
Nonalcoholic Fatty Liver

Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases with no approved treatment. Zonarol, an extract from brown algae, has been proven to have anti-inflammatory and antioxidant effects. In this study, we investigated the role of zonarol in the progression of methionine- and choline-deficiency (MCD) diet-induced NAFLD in mice. After oral treatment with zonarol, a lighter body weight was observed in zonarol group (ZG) mice in comparison to control group (CG) mice. The NAFLD scores of ZG mice were lower than those of CG mice. Hepatic and serum lipid levels were also lower in ZG mice with the reduced expression of lipid metabolism-related factors. Furthermore, ZG mice showed less lipid deposition, less inflammatory cell infiltration and lower inflammatory cytokine levels in comparison to CG mice. Moreover, the numbers of 8-hydroxy-20-deoxyguanosine (8-OHdG)-positive hepatocytes and levels of hepatic and serum thiobarbituric acid reactive substances (TBARS) were significantly lower in comparison to CG mice. The expression levels of nuclear factor erythroid 2 related factor 2 (Nrf2), as well as its upstream and downstream molecules, changed in ZG mice. Zonarol could prevent the progression of NAFLD by decreasing inflammatory responses, oxidative stress and improving lipid metabolism. Meanwhile the Nrf2 pathway may play an important role in these effects

Simultaneous co-assembly of fenofibrate and ketoprofen peptide for the dual-targeted treatment of nonalcoholic fatty liver disease (NAFLD)

2020 ◽  
Vol 56 (36) ◽  
pp. 4922-4925 ◽  
Author(s):  
Zhongyan Wang ◽  
Chuanrui Ma ◽  
Yuna Shang ◽  
Lijun Yang ◽  
Jing Zhang ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Lipid Accumulation ◽  
Fatty Liver Disease ◽  
Inflammatory Responses ◽  
Targeted Treatment ◽  
Nonalcoholic Fatty Liver ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation

An ingenious co-assembled nanosystem based on fenofibrate and ketoprofen peptide for the dual-targeted treatment of NAFLD by reducing hepatic lipid accumulation and inflammatory responses.

scholarly journals Impact of the Co-Administration of N-3 Fatty Acids and Olive Oil Components in Preclinical Nonalcoholic Fatty Liver Disease Models: A Mechanistic View

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 499 ◽  
Author(s):  
Rodrigo Valenzuela ◽  
Luis A. Videla
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Olive Oil ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Liver Steatosis ◽  
Virgin Olive Oil ◽  
Nonalcoholic Fatty Liver

Nonalcoholic fatty liver disease (NAFLD) is present in approximately 25% of the population worldwide. It is characterized by the accumulation of triacylglycerol in the liver, which can progress to steatohepatitis with different degrees of fibrosis, stages that lack approved pharmacological therapies and represent an indication for liver transplantation with consistently increasing frequency. In view that hepatic steatosis is a reversible condition, effective strategies preventing disease progression were addressed using combinations of natural products in the preclinical high-fat diet (HFD) protocol (60% of fat for 12 weeks). Among them, eicosapentaenoic acid (C20:5n-3, EPA) and docosahexaenoic acid (C22:5n-3, DHA), DHA and extra virgin olive oil (EVOO), or EPA plus hydroxytyrosol (HT) attained 66% to 83% diminution in HFD-induced steatosis, with the concomitant inhibition of the proinflammatory state associated with steatosis. These supplementations trigger different molecular mechanisms that modify antioxidant, antisteatotic, and anti-inflammatory responses, and in the case of DHA and HT co-administration, prevent NAFLD. It is concluded that future studies in NAFLD patients using combined supplementations such as DHA plus HT are warranted to prevent liver steatosis, thus avoiding its progression into more unmanageable stages of the disease.

scholarly journals Deficiency in Galectin-3 Promotes Hepatic Injury in CDAA Diet-Induced Nonalcoholic Fatty Liver Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Kazuhiro Nomoto ◽  
Takeshi Nishida ◽  
Yuko Nakanishi ◽  
Makoto Fujimoto ◽  
Ichiro Takasaki ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Hepatic Injury ◽  
Inflammatory Responses ◽  
Expression Profiles ◽  
Severe Form ◽  
Nonalcoholic Fatty Liver ◽  
Galectin 3

Nonalcoholic fatty liver disease (NAFLD) is increasingly recognized as a condition in which excess fat accumulates in hepatocytes. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD in which inflammation and fibrosis in the liver are noted, may eventually progress to end-stage liver disease. Galectin-3, a β-galactoside-binding animal lectin, is a multifunctional protein. This protein is involved in inflammatory responses and carcinogenesis. We investigated whether galectin-3 is involved in the development of NASH by comparing galectin-3 knockout (gal3−/−) mice and wild-type (gal3+/+) mice with choline-deficient L-amino-acid-defined (CDAA) diet-induced NAFLD/NASH. Hepatic injury was significantly more severe in thegal3−/−male mice, as compared to thegal3+/+mice. Data generated by microarray analysis of gene expression suggested that galectin-3 deficiency causes alterations in the expression of various genes associated with carcinogenesis and lipid metabolism. Through canonical pathway analysis, involvement of PDGF and IL-6 signaling pathways was suggested in galectin-3 deficiency. Significant increase of CD14, Fos, and Jun, those that were related to lipopolysaccharide-mediated signaling, was candidate to promote hepatocellular damages in galectin-3 deficiency. In conclusion, galectin-3 deficiency in CDAA diet promotes NAFLD features. It may be caused by alterations in the expression profiles of various hepatic genes including lipopolysaccharide-mediated inflammation.

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