Maternal High-Fat Diet Programs Renal Peroxisomes and Activates NLRP3 Inflammasome-Mediated Pyroptosis in the Rat Fetus

We evaluate the effects of the Chaihu-Shugan-San decoction on intestinal microbe dysbiosis and chronic metabolic inflammation via the NLRP3 pathway in NAFLD rats that were fed a high-fat diet. Twenty-four SD rats (male, six weeks old, 200 ± 20 g) were randomly divided into three groups: normal control group (NC group), high-fat diet-fed group (HFD group), and Chaihu-Shugan-San decoction intervention group (CH group). The NC group rats were given standard feed, the HFD group rats were all fed a high-fat diet (83% standard feed + 10% lard oil + 5% sucrose + 1.5% cholesterol + 0.5% cholate), and the CH group rats were given a HFD plus Chaihu-Shugan-San at 9.6 g•kg−1•d−1. Body composition, serum and liver lipids, inflammatory markers, intestinal microbial population, and the NLRP3 pathway-associated protein were assessed. The results showed that Chaihu-Shugan-San decoction significantly reduced body weight and total fat mass and the levels of serum LPS, TG, TNF-α, IL-1β, and IL-18, as well as liver TC, TG, TNF-α, IL-1β, and IL-18 (P <0.05). The abundance of Enterobacteriaceae (0.375% versus 0.064%,P< 0.05), Staphylococcaceae families (0.049% versus 0.016%,P< 0.05) andVeillonellagenus (0.096% versus 0.009%,P <0.01) significantly decreased, whereas the abundance ofAnaeroplasmagenus (0.0005% versus 0.0178%,P <0.01) significantly increased. The expression levels of NLRP3, ASC, and Caspase-1 were changed significantly (P< 0.05). In summary, the Chaihu-Shugan-San decoction modulated intestinal microbe dysbiosis, reduced fat accumulation, and alleviated inflammatory factor expression, which are all processes related to the NLRP3 inflammasome pathway in NAFLD rats.

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Liraglutide protects non-alcoholic fatty liver disease via inhibiting NLRP3 inflammasome activation in a mouse model induced by high-fat diet

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2018.09.134 ◽

2018 ◽

Vol 505 (2) ◽

pp. 523-529 ◽

Cited By ~ 15

Author(s):

Wei Zhu ◽

Pan-Pan Feng ◽

Kun He ◽

Sheng-Wei Li ◽

Jian-Ping Gong

Keyword(s):

Liver Disease ◽

Mouse Model ◽

Nlrp3 Inflammasome ◽

High Fat Diet ◽

Fatty Liver Disease ◽

Inflammasome Activation ◽

High Fat ◽

Alcoholic Fatty Liver ◽

Nlrp3 Inflammasome Activation ◽

Alcoholic Fatty Liver Disease

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Deficiency of the Purinergic Receptor 2X7 Attenuates Nonalcoholic Steatohepatitis Induced by High-Fat Diet: Possible Role of the NLRP3 Inflammasome

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/8962458 ◽

2017 ◽

Vol 2017 ◽

pp. 1-14 ◽

Cited By ~ 5

Author(s):

Claudia Blasetti Fantauzzi ◽

Stefano Menini ◽

Carla Iacobini ◽

Chiara Rossi ◽

Eleonora Santini ◽

...

Keyword(s):

Nonalcoholic Steatohepatitis ◽

Nlrp3 Inflammasome ◽

High Fat Diet ◽

Molecular Mechanisms ◽

Purinergic Receptor ◽

High Fat ◽

Liver Sinusoidal Endothelial Cells ◽

Nonalcoholic Fatty Liver ◽

Markers Of Inflammation

Molecular mechanisms driving transition from simple steatosis to nonalcoholic steatohepatitis (NASH), a critical step in the progression of nonalcoholic fatty liver disease (NAFLD) to cirrhosis, are poorly defined. This study aimed at investigating the role of the purinergic receptor 2X7 (PR2X7), through the NLRP3 inflammasome, in the development of NASH. To this end, mice knockout for the Pr2x7 gene (Pr2x7−/−) and coeval wild-type (WT) mice were fed a high-fat diet (HFD) or normal-fat diet for 16 weeks. NAFLD grade and stage were lower in Pr2x7−/− than WT mice, and only 1/7 Pr2x7−/− animals showed evidence of NASH, as compared with 4/7 WT mice. Molecular markers of inflammation, oxidative stress, and fibrosis were markedly increased in WT-HFD mice, whereas no or significantly reduced increments were detected in Pr2x7−/− animals, which showed also decreased modulation of genes of lipid metabolism. Deletion of Pr2x7 gene was associated with blunted or abolished activation of NLRP3 inflammasome and expression of its components, which were induced in liver sinusoidal endothelial cells challenged with appropriate stimuli. These data show that Pr2x7 gene deletion protects mice from HFD-induced NASH, possibly through blunted activation of NLRP3 inflammasome, suggesting that PR2X7 and NLRP3 may represent novel therapeutic targets.

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Myeloid cell neuropilin 1 ameliorates high-fat diet-induced insulin resistance via suppression of Nlrp3 inflammasome

Macrophage ◽

10.14800/macrophage.1594 ◽

2018 ◽

Vol 4 ◽

Cited By ~ 1

Keyword(s):

Insulin Resistance ◽

Nlrp3 Inflammasome ◽

High Fat Diet ◽

Myeloid Cell ◽

High Fat ◽

Neuropilin 1

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

The Journal of Pathology ◽

10.1002/path.4237 ◽

2013 ◽

Vol 231 (3) ◽

pp. 342-353 ◽

Cited By ~ 70

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

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

Scientific Reports ◽

10.1038/s41598-021-98437-3 ◽

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.

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