Down Regulated XIAP Promotes Long-Term High Fat Diet-Stimulated NAFLD Through NLRP3 Inflammasome Activation and Oxidative Stress Signaling

2019 ◽  
Author(s):  
Minxuan Xu ◽  
Ge Chenxu ◽  
Qin Yuting ◽  
Gu Tingting ◽  
Deshuai Lou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nlrp3 Inflammasome ◽  
High Fat Diet ◽  
Inflammasome Activation ◽  
Stress Signaling ◽  
High Fat ◽  
Nlrp3 Inflammasome Activation ◽  
And Oxidative Stress

scholarly journals Salidroside Attenuates High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease via AMPK-Dependent TXNIP/NLRP3 Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-17 ◽  
Author(s):  
Tao Zheng ◽  
Xiaoyan Yang ◽  
Wenjin Li ◽  
Qibin Wang ◽  
Li Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Insulin Sensitivity ◽  
Nlrp3 Inflammasome ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Inflammasome Activation ◽  
High Fat ◽  
Nonalcoholic Fatty Liver ◽  
Nlrp3 Inflammasome Activation

Our previous studies suggested that salidroside could alleviate hepatic steatosis in type 2 diabetic C57BLKS/Leprdb (db/db) mice. The aim of the present study was to evaluate the therapeutic effect of salidroside on high-fat diet- (HFD-) induced nonalcoholic fatty liver disease (NAFLD) by investigating underlying mechanisms. Mice were fed with HFD or regular diet, randomly divided into two groups, and treated with salidroside or vehicle for 8 weeks. Then, biochemical analyses and histopathological examinations were conducted in vivo and in vitro. Salidroside administration attenuated HFD-induced obesity, blood glucose variability, and hepatic lipid deposition, markedly increasing insulin sensitivity in HFD mice. In addition, salidroside suppressed oxidative stress, thioredoxin-interacting protein (TXNIP) expression, and NLRP3 inflammasome activation in the liver. In cultured hepatocytes, salidroside dose dependently regulated lipid accumulation, reactive oxygen species (ROS) generation, and NLRP3 inflammasome activation as well as improved AMP-activated protein kinase (AMPK) activity and insulin sensitivity. The inhibition of AMPK activation by inhibitor or short interfering RNA (siRNA) resulted in the suppression of the beneficial effects of salidroside in hepatocytes. Our findings demonstrated that salidroside protects against NAFLD by improving hepatic lipid metabolism and NLRP3 inflammasome activation, and these actions are related to the regulation of the oxidative stress and AMPK-dependent TXNIP/NLRP3 pathways.

The purinergic 2X7receptor participates in renal inflammation and injury induced by high-fat diet: possible role of NLRP3 inflammasome activation

2013 ◽  
Vol 231 (3) ◽  
pp. 342-353 ◽  
Author(s):  
Anna Solini ◽  
Stefano Menini ◽  
Chiara Rossi ◽  
Carlo Ricci ◽  
Eleonora Santini ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
High Fat Diet ◽  
Inflammasome Activation ◽  
High Fat ◽  
Renal Inflammation ◽  
Nlrp3 Inflammasome Activation

scholarly journals The selective NLRP3 inhibitor MCC950 hinders atherosclerosis development by attenuating inflammation and pyroptosis in macrophages

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wenyun Zeng ◽  
Danbin Wu ◽  
Yingxin Sun ◽  
Yanrong Suo ◽  
Qun Yu ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
High Fat Diet ◽  
In Vitro Study ◽  
Inflammasome Activation ◽  
Mrna Levels ◽  
High Fat ◽  
Nlrp3 Inflammasome Activation ◽  
Atherosclerosis Development

AbstractNLRP3 inflammasome is a vital player in macrophages pyroptosis, which is a type of proinflammatory cell-death and takes part in the pathogenesis of atherosclerosis. In this study, we used apoE−/− mice and ox-LDL induced THP-1 derived macrophages to explore the mechanisms of MCC950, a selective NLRP3 inhibitor in treating atherosclerosis. For the in vivo study, MCC950 was intraperitoneal injected to 8-week-old apoE−/− mice fed with high-fat diet for 12 weeks. For the in vitro study, THP-1 derived macrophages were treated with ox-LDL and MCC950 for 48 h. MCC950 administration reduced plaque areas and macrophages contents, but did not improve the serum lipid profiles in aortic root of apoE−/− mice. MCC950 inhibited the activation of NLRP3/ASC/Caspase-1/GSDMD-N axis, and alleviated macrophages pyroptosis and the production of IL-1β and IL-18 both in aorta and in cell lysates. However, MCC950 did not affect the expression of TLR4 or the mRNA levels of NLRP3 inflammasome and its downstream proteins, suggesting that MCC950 had no effects on the priming of NLRP3 inflammasome activation in macrophages. The anti-atherosclerotic mechanisms of MCC950 on attenuating macrophages inflammation and pyroptosis involved in inhibiting the assembly and activation of NLRP3 inflammasome, rather than interrupting its priming.

scholarly journals Deoxycholic Acid-Mediated Sphingosine-1-Phosphate Receptor 2 Signaling Exacerbates DSS-Induced Colitis through Promoting Cathepsin B Release

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Shengnan Zhao ◽  
Zizhen Gong ◽  
Xixi Du ◽  
Chunyan Tian ◽  
Lingyu Wang ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
High Fat Diet ◽  
Cathepsin B ◽  
Intestinal Inflammation ◽  
Critical Role ◽  
Inflammasome Activation ◽  
High Fat ◽  
Molecular Pattern ◽  
Nlrp3 Inflammasome Activation ◽  
Sphingosine 1 Phosphate

We recently have proved that excessive fecal DCA caused by high-fat diet may serve as an endogenous danger-associated molecular pattern to activate NLRP3 inflammasome and thus contributes to the development of inflammatory bowel disease (IBD). Moreover, the effect of DCA on inflammasome activation is mainly mediated through bile acid receptor sphingosine-1-phosphate receptor 2 (S1PR2); however, the intermediate process remains unclear. Here, we sought to explore the detailed molecular mechanism involved and examine the effect of S1PR2 blockage in a colitis mouse model. In this study, we found that DCA could dose dependently upregulate S1PR2 expression. Meanwhile, DCA-induced NLRP3 inflammasome activation is at least partially achieved through stimulating extracellular regulated protein kinases (ERK) signaling pathway downstream of S1PR2 followed by promoting of lysosomal cathepsin B release. DCA enema significantly aggravated DSS-induced colitis in mice and S1PR2 inhibitor as well as inflammasome inhibition by cathepsin B antagonist substantially reducing the mature IL-1β production and alleviated colonic inflammation superimposed by DCA. Therefore, our findings suggest that S1PR2/ERK1/2/cathepsin B signaling plays a critical role in triggering inflammasome activation by DCA and S1PR2 may represent a new potential therapeutic target for the management of intestinal inflammation in individuals on a high-fat diet.

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