scholarly journals Stk24 protects against obesity-associated metabolic disorders by disrupting the NLRP3 inflammasome

Cell Reports ◽  
2021 ◽  
Vol 35 (8) ◽  
pp. 109161
Author(s):  
Qiang Qin ◽  
Jia’nan Shou ◽  
Mengjie Li ◽  
Meidi Gu ◽  
Zhuoxian Meng ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Metabolic Disorders

scholarly journals The NLRP3 Inflammasome as a Novel Player of the Intercellular Crosstalk in Metabolic Disorders

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Elisa Benetti ◽  
Fausto Chiazza ◽  
Nimesh S. A. Patel ◽  
Massimo Collino
Keyword(s):  
Chronic Inflammation ◽  
Nlrp3 Inflammasome ◽  
Metabolic Disorders ◽  
Inflammasome Activation ◽  
Nucleotide Binding Domain ◽  
Metabolic Inflammation ◽  
Nlrp3 Inflammasome Activation ◽  
Leucine Rich Repeat Protein

The combination of obesity and type 2 diabetes is a serious health problem, which is projected to afflict 300 million people worldwide by 2020. Both clinical and translational laboratory studies have demonstrated that chronic inflammation is associated with obesity and obesity-related conditions such as insulin resistance. However, the precise etiopathogenetic mechanisms linking obesity to diabetes remain to be elucidated, and the pathways that mediate this phenomenon are not fully characterized. One of the most recently identified signaling pathways, whose activation seems to affect many metabolic disorders, is the “inflammasome,” a multiprotein complex composed of NLRP3 (nucleotide-binding domain and leucine-rich repeat protein 3), ASC (apoptosis-associated speck-like protein containing a CARD), and procaspase-1. NLRP3 inflammasome activation leads to the processing and secretion of the proinflammatory cytokines interleukin- (IL-) 1βand IL-18. The goal of this paper is to review new insights on the effects of the NLRP3 inflammasome activation in the complex mechanisms of crosstalk between different organs, for a better understanding of the role of chronic inflammation in metabolic disease pathogenesis. We will provide here a perspective on the current research on NLRP3 inflammasome, which may represent an innovative therapeutic target to reverse the detrimental metabolic consequences of the metabolic inflammation.

Lycopene Ameliorates Atrazine-Induced Pyroptosis in Spleen via Suppressing the Ox-mtDNA/Nlrp3 Inflammasome Pathway

2021 ◽  
Author(s):  
Shi-Yong Zhu ◽  
Jian-Ying Guo ◽  
Jin-Yang Li ◽  
Xueyan Dai ◽  
Xue-Nan Li ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Metabolic Disorders ◽  
Cellular Stress ◽  
Integration Point ◽  
Extracellular Stimuli

Nlrp3 is a vital integration point of diverse extracellular stimuli and cellular stress. However, inappropriate activation of Nlrp3 results in progression of autoinflammatory and metabolic disorders. Atrazine, using widely in...

scholarly journals Salvianolic Acid A Ameliorates Early-Stage Atherosclerosis Development by Inhibiting NLRP3 Inflammasome Activation in Zucker Diabetic Fatty Rats

Molecules ◽  
2020 ◽  
Vol 25 (5) ◽  
pp. 1089 ◽  
Author(s):  
Quanxin Ma ◽  
Qinqin Yang ◽  
Jiaojiao Chen ◽  
Chen Yu ◽  
Lizong Zhang ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Metabolic Disorders ◽  
Salvia Miltiorrhiza ◽  
Blood Cholesterol ◽  
Inflammasome Activation ◽  
Salvianolic Acid ◽  
Salvianolic Acid A ◽  
Zucker Diabetic Fatty Rats ◽  
Zdf Rats ◽  
Anti Inflammatory

Salvianolic acid A (SAA), an important bioactive polyphenolic acid found in Salvia miltiorrhiza Bunge, may be used for treating metabolic disorders due to its anti-inflammatory activity. Since chronic inflammation plays an important role in type 2 diabetes mellitus (T2DM) complicated with atherosclerosis (AS), SAA may have beneficial effects on AS. Here, we evaluated the effects of SAA on metabolic disorders in male Zucker diabetic fatty (ZDF) rats induced by a high-fat diet and Vitamin D3 injections. Compared with the model group, the SAA high dosage (1 mg/kg) group exhibited decreased hemoglobin A1C levels but unchanged blood glucose levels. The disrupted lipid profiles were ameliorated by SAA, with significantly decreased levels of blood cholesterol, LDL-C and triglyceride. The protective effects of SAA against early AS were further confirmed by histopathological examination of aortic tissues. In addition, we observed that SAA decreased serum hs-CRP levels and suppressed the activation of NLRP3 inflammasome and NF-κB signaling in aortic tissues of ZDF rats. Collectively, our results demonstrate the potential of SAA to alleviate AS and T2DM in ZDF rats as a result of its anti-inflammatory effects.

scholarly journals NLRP3 Inflammasome Activation in Adipose Tissues and Its Implications on Metabolic Diseases

2020 ◽  
Vol 21 (11) ◽  
pp. 4184 ◽  
Author(s):  
Kelvin Ka-Lok Wu ◽  
Samson Wing-Ming Cheung ◽  
Kenneth King-Yip Cheng
Keyword(s):  
Adipose Tissue ◽  
Nlrp3 Inflammasome ◽  
Metabolic Disorders ◽  
Immune Cell ◽  
Diabetic Patients ◽  
Inflammasome Activation ◽  
Low Grade ◽  
Adipose Tissues ◽  
Adipose Tissue Dysfunction ◽  
Nlrp3 Inflammasome Activation

Adipose tissue is an active endocrine and immune organ that controls systemic immunometabolism via multiple pathways. Diverse immune cell populations reside in adipose tissue, and their composition and immune responses vary with nutritional and environmental conditions. Adipose tissue dysfunction, characterized by sterile low-grade chronic inflammation and excessive immune cell infiltration, is a hallmark of obesity, as well as an important link to cardiometabolic diseases. Amongst the pro-inflammatory factors secreted by the dysfunctional adipose tissue, interleukin (IL)-1β, induced by the NLR family pyrin domain-containing 3 (NLRP3) inflammasome, not only impairs peripheral insulin sensitivity, but it also interferes with the endocrine and immune functions of adipose tissue in a paracrine manner. Human studies indicated that NLRP3 activity in adipose tissues positively correlates with obesity and its metabolic complications, and treatment with the IL-1β antibody improves glycaemia control in type 2 diabetic patients. In mouse models, genetic or pharmacological inhibition of NLRP3 activation pathways or IL-1β prevents adipose tissue dysfunction, including inflammation, fibrosis, defective lipid handling and adipogenesis, which in turn alleviates obesity and its related metabolic disorders. In this review, we summarize both the negative and positive regulators of NLRP3 inflammasome activation, and its pathophysiological consequences on immunometabolism. We also discuss the potential therapeutic approaches to targeting adipose tissue inflammasome for the treatment of obesity and its related metabolic disorders.

Endoplasmic reticulum stress and NLRP3 inflammasome: Crosstalk in cardiovascular and metabolic disorders

2019 ◽  
Vol 234 (9) ◽  
pp. 14773-14782 ◽  
Author(s):  
Ting Ji ◽  
Yuehu Han ◽  
Wenwen Yang ◽  
Baoping Xu ◽  
Meng Sun ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Nlrp3 Inflammasome ◽  
Metabolic Disorders

scholarly journals The Role of the Interplay Between Autophagy and NLRP3 Inflammasome in Metabolic Disorders

2021 ◽  
Vol 9 ◽  
Author(s):  
Shuangyu Lv ◽  
Honggang Wang ◽  
Xiaotian Li
Keyword(s):  
Nlrp3 Inflammasome ◽  
Metabolic Disorders ◽  
Interleukin 1 ◽  
Basic Research ◽  
Interleukin 1 Beta ◽  
Cell Composition ◽  
Pyrin Domain ◽  
Receptor Family ◽  
Oligomerization Domain

Autophagy is an important and conserved cellular pathway in which cells transmit cytoplasmic contents to lysosomes for degradation. It plays an important role in maintaining the balance of cell composition synthesis, decomposition and reuse, and participates in a variety of physiological and pathological processes. The nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome can induce the maturation and secretion of Interleukin-1 beta (IL-1β) and IL-18 by activating caspase-1. It is involved in many diseases. In recent years, the interplay between autophagy and NLRP3 inflammasome has been reported to contribute to many diseases including metabolic disorders related diseases. In this review, we summarized the recent studies on the interplay between autophagy and NLRP3 inflammasome in metabolic disorders to provide ideas for the relevant basic research in the future.

The NLRP3 inflammasome: Role in metabolic disorders and regulation by metabolic pathways

2018 ◽  
Vol 419 ◽  
pp. 8-19 ◽  
Author(s):  
Danlu Jiang ◽  
Sheng Chen ◽  
Ruyu Sun ◽  
Xue Zhang ◽  
Di Wang
Keyword(s):  
Nlrp3 Inflammasome ◽  
Metabolic Pathways ◽  
Metabolic Disorders

scholarly journals Role of NLRP3 Inflammasome Activation in Obesity-Mediated Metabolic Disorders

2021 ◽  
Vol 18 (2) ◽  
pp. 511
Author(s):  
Kaiser Wani ◽  
Hind AlHarthi ◽  
Amani Alghamdi ◽  
Shaun Sabico ◽  
Nasser M. Al-Daghri
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Nlrp3 Inflammasome ◽  
Metabolic Disorders ◽  
Metabolic Diseases ◽  
Protein Complexes ◽  
Inflammasome Activation ◽  
Low Grade ◽  
Nlrp3 Inflammasome Activation ◽  
Specific Inhibitors

NLRP3 inflammasome is one of the multimeric protein complexes of the nucleotide-binding domain, leucine-rich repeat (NLR)-containing pyrin and HIN domain family (PYHIN). When activated, NLRP3 inflammasome triggers the release of pro-inflammatory interleukins (IL)-1β and IL-18, an essential step in innate immune response; however, defective checkpoints in inflammasome activation may lead to autoimmune, autoinflammatory, and metabolic disorders. Among the consequences of NLRP3 inflammasome activation is systemic chronic low-grade inflammation, a cardinal feature of obesity and insulin resistance. Understanding the mechanisms involved in the regulation of NLRP3 inflammasome in adipose tissue may help in the development of specific inhibitors for the treatment and prevention of obesity-mediated metabolic diseases. In this narrative review, the current understanding of NLRP3 inflammasome activation and regulation is highlighted, including its putative roles in adipose tissue dysfunction and insulin resistance. Specific inhibitors of NLRP3 inflammasome activation which can potentially be used to treat metabolic disorders are also discussed.

scholarly journals Total Flavonoids of Glycyrrhiza uralensis Alleviates Irinotecan-Induced Colitis via Modification of Gut Microbiota and Fecal Metabolism

2021 ◽  
Vol 12 ◽  
Author(s):  
Shi-Jun Yue ◽  
Yi-Feng Qin ◽  
An Kang ◽  
Hui-Juan Tao ◽  
Gui-Sheng Zhou ◽  
...  
Keyword(s):  
Body Weight ◽  
Uric Acid ◽  
Gut Microbiota ◽  
Nlrp3 Inflammasome ◽  
Metabolic Disorders ◽  
Activity Index ◽  
The Body ◽  
Glycyrrhiza Uralensis ◽  
Uric Acid Concentration ◽  
Total Flavonoids

Irinotecan (CPT-11)-induced gastrointestinal toxicity strongly limits its anticancer efficacy. Glycyrrhiza uralensis Fisch., especially flavonoids, has strong anti-inflammatory and immunomodulatory activities. Herein, we investigate the protective effect of the total flavonoids of G. uralensis (TFGU) on CPT-11–induced colitis mice from the perspective of gut microbiota and fecal metabolism. The body weight and colon length of mice were measured. Our results showed that oral administration of TFGU significantly attenuated the loss of body weight and the shortening of colon length induced by CPT-11. The elevated disease activity index and histological score of colon as well as the up-regulated mRNA and protein levels of TNF-α, IL-1β, and IL-6 in the colonic tissue of CPT-11–treated mice were significantly decreased by TFGU. Meanwhile, TFGU restored the perturbed gut microbial structure and function in CPT-11–treated mice to near normal level. TFGU also effectively reversed the CPT-11–induced fecal metabolic disorders in mice, mainly call backing the hypoxanthine and uric acid in purine metabolism. Spearman’s correlation analysis further revealed that Lactobacillus abundance negatively correlated with fecal uric acid concentration, suggesting the pivotal role of gut microbiota in CPT-11–induced colitis. Since uric acid is a ligand of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, TFGU was further validated to inhibit the activation of NLRP3 inflammasome by CPT-11. Our findings suggest TFGU can correct the overall gut microbial dysbiosis and fecal metabolic disorders in the CPT-11–induced colitis mice, underscoring the potential of using dietary G. uralensis as a chemotherapeutic adjuvant.

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