Abstract
Nonalcoholic steatohepatitis (NASH) is a progressive, chronic liver disease worldwide which imposes a large economic burden on society. M1/M2 macrophage balance destruction and recruitment of mononuclear immune cells to the liver play critical roles in NASH. Several studies have shown that the expression of TNF-like ligand 1 aberrance (TL1A) increased in macrophages associated with many inflammatory diseases, for example, inflammatory bowel disease, primary biliary cholangitis, and liver fibrosis. One recent research showed that weight, abdominal adipose, and liver leptin, one of the critical fat cytokines, were reduced in TL1A knockout mice. However, the functional and molecular regulatory mechanisms of TL1A on macrophage polarization and recruitment in NASH have yet to be clarified. The authors found that high fructose high fat diet and methionine-choline deficiency diet induced the expression of TL1A in macrophages of liver tissue from murine NASH models. Myeloid-specific TL1A overexpressed mice showed exacerbated steatohepatitis with increased hepatic lipid accumulation, inflammation, liver injury, and apoptosis. M1 macrophages' infiltration and the production of proinflammatory and chemotactic cytokines increased in liver of NASH mouse models with myeloid-specific TL1A overexpressed. Furthermore, this paper revealed that bone marrow-derived macrophages and Kupffer cells with overexpression of TL1A exacerbated the lipid accumulation and expression of proinflammatory factors in the murine primary hepatocytes after free fatty acid treatment in vitro. In conclusion, TL1A-mediated M1-type macrophage polarization and recruitment into the liver promoted steatohepatitis in murine NASH.
Highlights
Nonalcoholic steatohepatitis (NASH) is an aggressive form of nonalcoholic fatty liver disease (NAFLD), which characterized by excessive fatty accumulation in liver, cell inflammation, and liver fibrosis
This paper evaluated the expression of tumor necrosis factor- (TNF-)like ligand 1 aberrance (TL1A) in liver tissues and macrophages to explore the association between TL1A and NASH
Consistent with the high fructose high fat diets (HFHF) model, increased chemokines and their receptors in Tg mice fed with methionine-choline deficiency (MCD) displayed severe infiltration (Figure 4(c)). These results suggested that myeloidspecific TL1A overexpression could enhance macrophage infiltration contributing to steatohepatitis in mice
Summary
Nonalcoholic steatohepatitis (NASH) is an aggressive form of nonalcoholic fatty liver disease (NAFLD), which characterized by excessive fatty accumulation in liver, cell inflammation, and liver fibrosis. Cirrhosis increases hepatocellular carcinoma (HCC) development risks [1, 2]. With the improvement of living standards and change of dietary habits, the morbidity of NASH gradually increases. It has become a major healthcare burden worldwide [3, 4]. The pathogenesis of NASH is multifactorial and remains incompletely defined. The investigation of NASH is of great necessity and significance
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