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 OP0277-PARE METABERN, THE EUROPEAN REFERENCE NETWORK FOR RARE HEREDITARY DISEASES: STRUCTURE, OBJECTIVES, METABOLIC RMDS AND THE ROLES OF EUROPEAN PATIENT ADVOCACY GROUPS (EPAGS)

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 168.2-168
Author(s):  
L. Wagner ◽  
S. Sestini ◽  
C. Brown ◽  
A. Finglas ◽  
R. Francisco ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Health Care ◽  
Social Science ◽  
Metabolic Pathways ◽  
Metabolic Disorders ◽  
Clinical Care ◽  
Single Point ◽  
Link Type ◽  
The Impact

Background:Inborn metabolic disorders (IMDs) currently encompass more than 1,500 diseases with new ones still to be identified1. Each of them is characterised by a genetic defect affecting a metabolic pathway. Only few of them have curative treatments, that target the respective metabolic pathway. Commonly, treatment examples include diet, substrate reduction therapies, enzyme replacement therapies, gene therapy and biologicals, enabling IMD-patient now to survive to adulthood. About 30 % of all IMDs involve the musculoskeletal system and are here referred to as rare metabolic RMDs. Generally, IMDs are very heterogenous with respect to symptoms and severity, often being systemic and affecting more children than adults. Thus, challenges include certified advanced training of adult metabolic experts, standardised transition plans, social support and development of therapies for diseases that do not have any cure yet.Objectives:Introduction of MetabERN, its structure and objectives, highlighting on the unique features and challenges of metabolic RMDs and describing the involvement of patient representation in MetabERN.Methods:MetabERN is stratified in 7 subnetworks (SNW) according to the respective metabolic pathways and 9 work packages (WP), including administration, dissemination, guidelines, virtual counselling framework, research/clinical trials, continuity of care, education and patient involvement. The patient board involves a steering committee and single point of contacts for each subnetwork and work package, respectively2. Projects include identifying the need of implementing social science to assess the psycho-socio-economic burden of IMDs, webinars on IMDs and their transition as well as surveys on the impact of COVID-193 on IMD-patients and health care providers (HCPs), social assistance for IMD-patients and analysing the transition landscape within Europe.Results:The MetabERN structure enables bundling of expertise, capacity building and knowledge transfer for faster diagnosis and better health care. Rare metabolic RMDs are present in all SNWs that require unique treatments according to their metabolic pathways. Implementation of social science to assess the psycho-socio-economic burden of IMDs is still underused. Involvement of patient representatives is essential for a holistic healthcare not only focusing on clinical care, but also on the quality of life for IMD-patients. Surveys identified unmet needs of patient care, patients having little information on national support systems and structural deficits of healthcare systems to ensure HCP can provide adequate clinical care during transition phases. These results are collected by MetabERN and forwarded to the Directorate-General for Health and Food Safety (DG SANTE) of the European Commission (EC) to be addressed further.Conclusion:MetabERN offers an infrastructure of virtual healthcare for patients with IMDs. Thus, in collaboration with ERN ReCONNET, MetabERN can assist in identifying rare metabolic disorders of RMDs to shorten the odyssey of diagnosis and advise on their respective therapies. On the other hand, MetabERN can benefit from EULAR’s longstanding experience regarding issues affecting the quality of life, all RMD patients are facing, such as pain, stiffness, fatigue, rehabilitation, maintaining work and disability claims.References:[1]IEMbase - Inborn Errors of Metabolism Knowledgebase http://www.iembase.org/ (accessed Jan 29, 2021).[2]MetabERN: European Refence Network for Hereditary Metabolic Disorders https://metab.ern-net.eu/ (accessed Jan 29, 2021).[3]Lampe, C.; Dionisi-Vici, C.; Bellettato, C. M.; Paneghetti, L.; van Lingen, C.; Bond, S.; Brown, C.; Finglas, A.; Francisco, R.; Sestini, S.; Heard, J. M.; Scarpa, M.; MetabERN collaboration group. The Impact of COVID-19 on Rare Metabolic Patients and Healthcare Providers: Results from Two MetabERN Surveys. Orphanet J. Rare Dis.2020, 15 (1), 341. https://doi.org/10.1186/s13023-020-01619-x.Acknowledgements:The authors thank the MetabERN collaboration group, the single point of contacts (SPOC) of the MetabERN patient board and the Transition Project Working Group (TPWG)Disclosure of Interests:None declared

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.

Le acidure organiche

1996 ◽  
Vol 9 (6) ◽  
pp. 769-774 ◽  
Author(s):  
L. D'Incerti ◽  
L. Farina ◽  
I. Moroni ◽  
G. Uziel ◽  
M. Savoiardo
Keyword(s):  
Metabolic Pathways ◽  
Metabolic Disorders ◽  
Subcortical White Matter ◽  
Neurological Damage ◽  
Biochemical Tests ◽  
Organic Acidurias ◽  
Basal Nuclei ◽  
Progressive Encephalopathy ◽  
Liver And Kidney ◽  
Neurological Features

Organic acidurias are congenital metabolic disorders variously involving the metabolic pathways, mainly the catabolism of aminoacids and fatty acids with accumulation of one or more organic acids in blood or urine. This group of diseases includes over 50 specific forms which, although rare, are the most common cause of acute encephalopathy in infancy. Single or recurrent episodes of metabolic failure are the most frequent presenting symptom in infancy, often in the first weeks of life. Onset may also occur later with features of chronic encephalopathy and complex clinical features including seizures, dystonia, hypotonia and in some cases myopathies associated with liver and kidney failure. Early diagnosis of acute forms is important since some organic acidurias can be treated thus preventing often fatal episodes of metabolic failure or ongoing neurological damage. Definitive diagnosis requires a search for pathological metabolites in urine using gas chromatography and mass spectroscopy and confirmation of enzyme deficit. Neurological investigation will show features indicative of metabolic disease in acute forms and in children presenting with progressive encephalopathy. Neurological features are heterogeneous, but MR findings will offer information for subsequent biochemical tests and sometimes suggest diagnosis, especially signal changes in the basal nuclei and subcortical white matter.

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 Metabolic Signaling into Chromatin Modifications in the Regulation of Gene Expression

2018 ◽  
Vol 19 (12) ◽  
pp. 4108 ◽  
Author(s):  
Tian Gao ◽  
Zyanya Díaz-Hirashi ◽  
Francisco Verdeguer
Keyword(s):  
Metabolic Pathways ◽  
Metabolic Disorders ◽  
Regulation Of Gene Expression ◽  
Hormonal Control ◽  
The Other ◽  
Specific Gene ◽  
Chromatin Modifications ◽  
Metabolic Signaling ◽  
Adenosyl Methionine ◽  
Chromatin Acetylation

The regulation of cellular metabolism is coordinated through a tissue cross-talk by hormonal control. This leads to the establishment of specific transcriptional gene programs which adapt to environmental stimuli. On the other hand, recent advances suggest that metabolic pathways could directly signal into chromatin modifications and impact on specific gene programs. The key metabolites acetyl-CoA or S-adenosyl-methionine (SAM) are examples of important metabolic hubs which play in addition a role in chromatin acetylation and methylation. In this review, we will discuss how intermediary metabolism impacts on transcription regulation and the epigenome with a particular focus in metabolic disorders.

scholarly journals Gut Flora Mediated Mouse Metabolic Health Risk Caused by Dietary Exposure of Acetamiprid and Tebuconazole

2020 ◽  
Author(s):  
Liu Jingkun ◽  
Fangfang Zhao ◽  
Yanyang Xu ◽  
Nan Li ◽  
Jing Qiu ◽  
...  
Keyword(s):  
Health Risk ◽  
Metabolic Profiling ◽  
Metabolic Pathways ◽  
Metabolic Disorders ◽  
Pesticide Exposure ◽  
Intestinal Flora ◽  
Metabolic Health ◽  
Gut Flora ◽  
Low Level

Abstract Background:Dietary pesticide residue is an important dietary inducement of metabolic syndrome. Results:Chronic inflammation, insulin resistance, obesity, and non-alcoholic fatty liver disease were induced to tested mice through long-term and low-level of acetamiprid and tebuconazole. On the basis of these phenotypes, the mouse gut flora with metabolites, host circulation metabolic profiling, and their interrelations were investigated, and host metabolic pathways were detected. Results showed that pesticide exposure differently altered the abundance of gut microbial species, such as high ratio of Firmicutes/Bacteroidetes and increased high lipopolysaccharide-production species. Correlation analysis between gut flora and its metabolic profiling further explained these changes and their associations. Under these influences, metabolic profiling of host serum and liver was performed, and metabolic disorders were characterized. The relationships between serum and gut flora were determined via their significantly different metabolites. Alterations to the metabolic pathways of liver were clarified to deeply explore the influences on host physiology. Host metabolic disorders were evidently released by fructooligosaccharide and fecal microbiota transplantation intervention, directly proving that gut flora is a vital medium in metabolic health risk caused by pesticide exposure.Conclusion:Dietary long-term and low-level pesticides threated metabolic health via affecting intestinal flora. Metabolism of intestinal flora and host were all stressed by the exposure, and their alterations were in close proximity. Dietary interventions mitigated metabolic diseases via improving disorder of intestinal flora. This work supplied theoretical bases and intervention approaches to body metabolic problems caused by pesticides exposure on the basis of gut flora.

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