scholarly journals The ATP-P2X7 Signaling Axis Is Dispensable for Obesity-Associated Inflammasome Activation in Adipose Tissue

Diabetes ◽  
2012 ◽  
Vol 61 (6) ◽  
pp. 1471-1478 ◽  
Author(s):  
S. Sun ◽  
S. Xia ◽  
Y. Ji ◽  
S. Kersten ◽  
L. Qi
Keyword(s):  
Adipose Tissue ◽  
Inflammasome Activation ◽  
Signaling Axis

scholarly journals The phytochemical hyperforin triggers thermogenesis in adipose tissue via a Dlat-AMPK signaling axis to curb obesity

2021 ◽  
Vol 33 (3) ◽  
pp. 565-580.e7
Author(s):  
Suzhen Chen ◽  
Xiaoxiao Liu ◽  
Chao Peng ◽  
Chang Tan ◽  
Honglin Sun ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Ampk Signaling ◽  
Signaling Axis

scholarly journals Eplerenone prevented obesity-induced inflammasome activation and glucose intolerance

2017 ◽  
Vol 235 (3) ◽  
pp. 179-191 ◽  
Author(s):  
Tsutomu Wada ◽  
Akari Ishikawa ◽  
Eri Watanabe ◽  
Yuto Nakamura ◽  
Yusuke Aruga ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Glucose Intolerance ◽  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
M2 Macrophage ◽  
Expression Levels ◽  
Nlrp3 Inflammasome Activation ◽  
M1 Macrophage ◽  
Anti Inflammatory

Obesity-associated activation of the renin-angiotensin-aldosterone system is implicated in the pathogenesis of insulin resistance; however, influences of mineralocorticoid receptor (MR) inhibition remain unclear. Therefore, we aimed to clarify the anti-inflammatory mechanisms of MR inhibition using eplerenone, a selective MR antagonist, in C57BL/6 mice fed a high-fat diet (HFD) for 12 weeks. Eplerenone prevented excessive body weight gain and fat accumulation, ameliorated glucose intolerance and insulin resistance and enhanced energy metabolism. In the epididymal white adipose tissue (eWAT), eplerenone prevented obesity-induced accumulation of F4/80+CD11c+CD206−-M1-adipose tissue macrophage (ATM) and reduction of F4/80+CD11c−CD206+-M2-ATM. Interestingly, M1-macrophage exhibited lower expression levels of MR, compared with M2-macrophage, in the ATM of eWAT and in vitro-polarized bone marrow-derived macrophages (BMDM). Importantly, eplerenone and MR knockdown attenuated the increase in the expression levels of proIl1b, Il6 and Tnfa, in the eWAT and liver of HFD-fed mice and LPS-stimulated BMDM. Moreover, eplerenone suppressed IL1b secretion from eWAT of HFD-fed mice. To reveal the anti-inflammatory mechanism, we investigated the involvement of NLRP3-inflammasome activation, a key process of IL1b overproduction. Eplerenone suppressed the expression of the inflammasome components, Nlrp3 and Caspase1, in the eWAT and liver. Concerning the second triggering factors, ROS production and ATP- and nigericin-induced IL1b secretion were suppressed by eplerenone in the LPS-primed BMDM. These results indicate that eplerenone inhibited both the priming and triggering signals that promote NLRP3-inflammasome activation. Therefore, we consider MR to be a crucial target to prevent metabolic disorders by suppressing inflammasome-mediated chronic inflammation in the adipose tissue and liver under obese conditions.

scholarly journals Drosophila PDGF/VEGF signaling from muscles to hepatocyte-like cells protects against obesity

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Arpan C Ghosh ◽  
Sudhir Gopal Tattikota ◽  
Yifang Liu ◽  
Aram Comjean ◽  
Yanhui Hu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Lipid Level ◽  
Lipid Synthesis ◽  
Tissue Lipid ◽  
Tor Signaling ◽  
Specific Expression ◽  
Signaling Axis ◽  
Organ Specific ◽  
Lipid Stores ◽  
Multicellular Organisms

PDGF/VEGF ligands regulate a plethora of biological processes in multicellular organisms via autocrine, paracrine, and endocrine mechanisms. We investigated organ-specific metabolic roles of Drosophila PDGF/VEGF-like factors (Pvfs). We combine genetic approaches and single-nuclei sequencing to demonstrate that muscle-derived Pvf1 signals to the Drosophila hepatocyte-like cells/oenocytes to suppress lipid synthesis by activating the Pi3K/Akt1/TOR signaling cascade in the oenocytes. Functionally, this signaling axis regulates expansion of adipose tissue lipid stores in newly eclosed flies. Flies emerge after pupation with limited adipose tissue lipid stores and lipid level is progressively accumulated via lipid synthesis. We find that adult muscle-specific expression of pvf1 increases rapidly during this stage and that muscle-to-oenocyte Pvf1 signaling inhibits expansion of adipose tissue lipid stores as the process reaches completion. Our findings provide the first evidence in a metazoan of a PDGF/VEGF ligand acting as a myokine that regulates systemic lipid homeostasis by activating TOR in hepatocyte-like cells.

scholarly journals Callicarpa Nudiflora Extract Exerts Anti-Inflammatory Effect on H. Pylori-Associated Gastritis Through Repression of ROS/NLRP3/Caspase-1/IL-1β Signaling Axis

2021 ◽  
Author(s):  
Lili Li ◽  
Xiaohui Zhu ◽  
Xingxing Chai ◽  
Xiaoyu Chen ◽  
Xiaohua Su ◽  
...  
Keyword(s):  
Cell Damage ◽  
Underlying Mechanism ◽  
Inflammatory Factors ◽  
Inflammasome Activation ◽  
Ros Production ◽  
Gastric Diseases ◽  
Caspase 1 ◽  
Signaling Axis ◽  
H Pylori

Abstract Helicobacter pylori ( H. pylori ) is a major pathogenic factor for the development of gastric diseases including chronic gastritis and gastric cancer. Callicarpa nudiflora (CN), an air-dried leaves extract of Callicarpa nudiflora Hook. & Arn., has been found to exhibit a broad-spectrum antibacterial effect. In our study, we extracted the active ingredient from air-dried leaves of Callicarpa nudiflora, detected the effect of CN against H. pylori -infected GES-1 cells in vitro , and elucidated the underlying mechanism. GES-1 cells were cocultured with HPSS1 at MOI = 100:1 and treated with different concentrations of CN. Results indicated that CN not only significantly decreased cellular lactate dehydrogenase leakage, but also markedly attenuated H. pylori -induced cell apoptosis and ROS production in GSE-1 cells, therefore protecting gastric epithelial cells against injuries caused by H. pylori . CN also inhibited the secretions of inflammatory factors, such as tumor necrosis factor-α (TNF-α), IL-1β, IL-6 and IL-8. Furthermore, CN remarkably decreased the expression levels of NLRP3, PYCARD, active Caspase-1. In conclusion, CN exhibited highly efficient protective effect against H. pylori -induced gastritis and cell damage; Mechanismly, CN suppressed H. pylori -triggered inflammatory response and pyroptosis through depressing ROS production and NLRP3 inflammasome activation via ROS/NLRP3/IL-1β signaling axis.

scholarly journals SYK-CARD9 Signaling Axis Promotes Gut Fungi-Mediated Inflammasome Activation to Restrict Colitis and Colon Cancer

Immunity ◽  
2018 ◽  
Vol 49 (3) ◽  
pp. 515-530.e5 ◽  
Author(s):  
Ankit Malik ◽  
Deepika Sharma ◽  
R.K. Subbarao Malireddi ◽  
Clifford S. Guy ◽  
Ti-Cheng Chang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Inflammasome Activation ◽  
Signaling Axis

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.

scholarly journals SIRT3 (Sirtuin-3) Prevents Ang II (Angiotensin II)–Induced Macrophage Metabolic Switch Improving Perivascular Adipose Tissue Function

2020 ◽  
Author(s):  
Tong Wei ◽  
Jing Gao ◽  
Chenglin Huang ◽  
Bei Song ◽  
Mengwei Sun ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Angiotensin Ii ◽  
Metabolic Phenotype ◽  
Inflammasome Activation ◽  
Ang Ii ◽  
Sirtuin 3 ◽  
Metabolic Switch ◽  
Brown Adipocytes ◽  
Perivascular Adipose Tissue

Objective: Infiltrated macrophages actively promote perivascular adipose tissue remodeling and represent a dominant population in the perivascular adipose tissue microenvironment of hypertensive mice. However, the role of macrophages in initiating metabolic inflammation remains uncertain. SIRT3 (sirtuin-3), a NAD-dependent deacetylase, is sensitive to metabolic status and mediates adaptation responses. In this study, we investigated the role of SIRT3-mediated metabolic shift in regulating NLRP3 (Nod-like receptor family pyrin domain-containing 3) inflammasome activation. Approach and Results: Here, we report that Ang II (angiotensin II) accelerates perivascular adipose tissue inflammation and fibrosis, accompanied by NLRP3 inflammasome activation and IL (interleukin)-1β secretion in myeloid SIRT3 knockout (SIRT3 − / − ) mice. This effect is associated with adipose tissue mitochondrial dysfunction. In vitro studies indicate that the deletion of SIRT3 in bone marrow–derived macrophages induces IL-1β production by shifting the metabolic phenotype from oxidative phosphorylation to glycolysis. Mechanistically, SIRT3 deacetylates and activates PDHA1 (pyruvate dehydrogenase E1 alpha) at lysine 83, and the loss of SIRT3 leads to PDH activity decrease and lactate accumulation. Knocking down LDHA (lactate dehydrogenase A) or using carnosine, a buffer against lactic acid, attenuates IL-1β secretion. Furthermore, the blockade of IL-1β from macrophages into brown adipocytes restores thermogenic markers and mitochondrial oxygen consumption. Moreover, NLRP3 knockout (NLRP3 −/− ) mice exhibited reduced IL-1β production while rescuing the mitochondrial function of brown adipocytes and alleviating perivascular adipose tissue fibrosis. Conclusions: SIRT3 represents a potential therapeutic target to attenuate NLRP3-related inflammation. Pharmacological targeting of glycolytic metabolism may represent an effective therapeutic approach.

scholarly journals The microbiome-adipose tissue axis in systemic metabolism

2020 ◽  
Vol 318 (4) ◽  
pp. G717-G724 ◽  
Author(s):  
Patrick Lundgren ◽  
Christoph A. Thaiss
Keyword(s):  
Adipose Tissue ◽  
Systemic Circulation ◽  
Microbial Colonization ◽  
Therapeutic Interventions ◽  
Intestinal Microbiome ◽  
Organ Systems ◽  
Host Health ◽  
Signaling Axis ◽  
Host Metabolism ◽  
Gain Access

The intestinal commensal microbiome is an important component of host health, in part by contributing an abundance of metabolites that gain access to the systemic circulation. The microbiome thereby influences the physiology of numerous organ systems outside the gastrointestinal tract. The consequences of this signaling axis between the intestinal microbiome and host are profound, in particular for the modulation of organismal metabolism. Here, we review recent examples whereby the intestinal microbiome influences host metabolism by influencing the biology of adipose tissue. We place a special emphasis on metabolite-driven pathways by which adipose tissue responds to alterations in intestinal microbial colonization. Given its accessibility for therapeutic interventions, the gut microbiome is an attractive relay module for the remote control of systemic metabolism.

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