Diverse Cytokines Secreted by Adipocyte in Linking Cardio-Metabolic Disorder and SLE DOI Creative Commons
Min Lai, Kai‐Hsin Lin, Xiaofang Chen

et al.

Frontiers in Bioscience-Landmark, Journal Year: 2024, Volume and Issue: 29(11)

Published: Oct. 31, 2024

Systemic lupus erythematosus (SLE) is a multi-factorial autoimmune-mediated disease with hyper-stimulation of immune cells especially the T lymphocytes. By this method, it might facilitate systematic damages in multiple tissues and organs. Otherwise, SLE also correlated diverse cardio-metabolic comorbidities, including dyslipidemia, insulin resistance, hypertension. It worth-noting that risk disorders significantly higher compared healthy patients which was reported as approximately one-third were proved obesity. Notably, current focus shifting to implementing protective strategies well elucidating underlying mechanisms lupus-mediated obese status. On other hand, adipocyte, most abundant endocrine cell fat tissue, are dysfunctional individuals aberrant secretion adipokines. proposing adipokine link pathology SLE, whereas related mechanism complicated. In review, functions potential by listed. Furthermore, recommendations, identify therapeutic targets for treatment summarized.

Language: Английский

Lipocalin-2-mediated astrocyte pyroptosis promotes neuroinflammatory injury via NLRP3 inflammasome activation in cerebral ischemia/reperfusion injury DOI Creative Commons
Juanji Li, Pengfei Xu, Ye Hong

et al.

Journal of Neuroinflammation, Journal Year: 2023, Volume and Issue: 20(1)

Published: June 23, 2023

Neuroinflammation is a vital pathophysiological process during ischemic stroke. Activated astrocytes play major role in inflammation. Lipocalin-2 (LCN2), secreted by activated astrocytes, promotes neuroinflammation. Pyroptosis pro-inflammatory form of programmed cell death that has emerged as new area research Nevertheless, the potential LCN2 astrocyte pyroptosis remains unclear.An stroke model was established middle cerebral artery occlusion (MCAO) vivo. In this study, vitro, oxygen-glucose deprivation and reoxygenation (O/R) were applied to cultured astrocytes. 24p3R (the receptor) inhibited astrocyte-specific adeno-associated virus (AAV-GFAP-24p3Ri). MCC950 Nigericin sodium salt (Nig) used inhibit or promote activation NLRP3 inflammasome pharmacologically, respectively. Histological biochemical analyses performed assess neuron death. Additionally, neurological deficits mice evaluated.LCN2 expression significantly induced 24 h after onset mouse MCAO model. Lcn2 knockout (Lcn2-/-) exhibited reduced infarct volume improved cognitive functions MCAO. its receptor colocalized Mechanistically, suppression AAV-GFAP-24p3Ri alleviated pyroptosis-related pore formation secretion cytokines via LCN2, which then reversed Nig-induced activation. Astrocyte exacerbated Lcn2-/- intracerebroventricular administration recombinant (rLCN2), while aggravation restricted blocking inhibiting with MCC950.LCN2/24p3R mediates following ischemia/reperfusion injury.

Language: Английский

Citations

42
Myeloid Trem2 ameliorates the progression of metabolic dysfunction-associated steatotic liver disease by regulating macrophage pyroptosis and inflammation resolution DOI Creative Commons
Wenjie Yu, Yu Zhang,

Linfeng Sun

et al.

Metabolism, Journal Year: 2024, Volume and Issue: 155, P. 155911 - 155911

Published: April 10, 2024

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing year by and has become one the leading causes end-stage worldwide. Triggering Receptor Expressed on Myeloid Cells 2 (Trem2) been confirmed to play an essential role in progression MASLD, but its specific mechanism still needs be clarified. This study aims explore Trem2 MASLD.

Language: Английский

Citations

10
The role and mechanism of m6A methylation in diabetic nephropathy DOI
Lin-Jing Yan, Liang Guo

Life Sciences, Journal Year: 2025, Volume and Issue: 363, P. 123355 - 123355

Published: Jan. 6, 2025

Language: Английский

Citations

1
Clinical and molecular profiling of human visceral adipose tissue reveals impairment of vascular architecture and remodeling as an early hallmark of dysfunction DOI Creative Commons
Daniela Rosendo‐Silva,

Pedro Bastos Gomes,

Tiago Rodrigues

et al.

Metabolism, Journal Year: 2024, Volume and Issue: 153, P. 155788 - 155788

Published: Jan. 18, 2024

Adipose tissue dysfunction is more related to insulin resistance than body mass index itself and an alteration in adipose function thought underlie the shift from metabolically healthy unhealthy obesity. Herein, we performed a clustering analysis that revealed distinct visceral gene expression patterns patients with obesity at stages of metabolic dysregulation. We have built cross-sectional cohort aims reflecting evolution sequelae main objective map sequential events play role (insulin-sensitive) state several incremental degrees dysregulation, encompassing establishment, pre-diabetes, type 2 diabetes. found mainly marked by downregulation vasculature remodeling-associated expression, suggesting processes like angiogenesis adaptative expansion/retraction ability suffer early Prediabetes was characterized compensatory growth factor-dependent signaling increased response hypoxia, while diabetes associated loss cellular hypoxia concomitant upregulation inflammatory markers. Our findings suggest putative sequence dysregulation biological not linear has multiple phases across process, ultimately culminating climax Several studies addressed transcriptomic changes However, best our knowledge, this first study unraveling potential molecular mechanisms multi-step along

Language: Английский

Citations

8
Neutrophil aging exacerbates high fat diet induced metabolic alterations DOI Creative Commons
Andrea Baragetti, Lorenzo Da Dalt, Annalisa Moregola

et al.

Metabolism, Journal Year: 2023, Volume and Issue: 144, P. 155576 - 155576

Published: April 26, 2023

Background High fat diet (HFD) chronically hyper-activates the myeloid cell precursors, but whether it affects neutrophil aging is unknown. Purpose We characterized how HFD impacts aging, infiltration in metabolic tissues and if this turn, modulates development of alterations. immunophenotyped neutrophils responses physiology (wild-type mice, WT) mice with constitutively aged (MRP8 driven conditional deletion CXCR4; herein CXCR4fl/flCre+) or fresh CXCR2; CXCR2fl/flCre+), following 20 weeks feeding (45 % kcal from fat). Findings After HFD, gluco-metabolic profile CXCR4fl/flCre+ was comparable to that WT while CXCR2fl/flCre+ were protected infiltrated more, less, liver visceral adipose tissue (VAT). As consequence, resulted into hepatic "suicidal" extracellular traps (NETs) altered immune architecture VAT, promoted proresolutive NETs reduced accumulation pro-inflammatory macrophages VAT. In humans, higher plasma levels Cxcl12 (CXCR4 ligand) correlated adiposity Cxcl1 (the ligand CXCR2) indexes steatosis, syndrome. Conclusions Neutrophil might contribute induced disorders.

Language: Английский

Citations

13
Effect of weight loss and liraglutide on neutrophil gelatinase-associated lipocalin levels among individuals with overweight and knee osteo-arthritis: Exploratory analyses of a randomized controlled trial DOI Creative Commons
Asbjørn S. Poulsen, Zara R. Stisen, Marie Skougaard

et al.

Osteoarthritis and Cartilage Open, Journal Year: 2025, Volume and Issue: 7(1), P. 100562 - 100562

Published: Jan. 5, 2025

Language: Английский

Citations

0
Resibufogenin protects against atherosclerosis in ApoE-/- mice through blocking NLRP3 inflammasome assembly DOI Creative Commons

Xiaoyang Chen,

Yijun Chen,

Zhai Chenguang

et al.

Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Atherosclerosis (AS), a major cause of cardiovascular diseases, is characterized by lipid accumulation and chronic inflammation within arterial walls. Traditional treatments, such as statins, are often ineffective for many patients, highlighting the need novel therapeutic strategies. This study explores potential Resibufogenin (RBG) an NLRP3 inflammasome inhibitor treating AS in ApoE-/- mice. We performed experiments encompassing cellular studies, animal model assessments, molecular simulations, binding assays to assess RBG's impact on inflammasome, inflammatory cytokine release, foam cell formation. RBG treatment alleviated mice, evidenced reduced body weight, smaller atherosclerotic plaques, improved serum profiles. Transcriptomics biology demonstrated that suppressed expression key markers NLRP3. also macrophage infiltration promoted polarization toward anti-inflammatory M2 phenotype. Molecular docking, SPR, Pull-down studies identified non-covalent interaction between CYS-279 residue NLRP3, confirming its role potent inhibitor. effectively inhibits activation, reduces pro-inflammatory decreases formation foamy macrophages, thereby slowing progression AS. Although these findings highlight promising approach further research necessary safety effectiveness humans investigate possible synergistic effects with other treatments.

Language: Английский

Citations

0
Activation of CXCR7 exerts an inhibitory effect on adipogenesis through regulation of β-arrestin2/Wnt and AKT signalling DOI Creative Commons

Shiyue Sun,

Muhammad Arif Aslam, Eun Bi

et al.

Adipocyte, Journal Year: 2025, Volume and Issue: 14(1)

Published: April 29, 2025

CXCR7, an alternative receptor for the inflammatory chemokine SDF-1, is involved in cell proliferation and migration. Recent studies have reported that CXCR7 also plays a role adipose tissue. However, evidence regarding of its ligands adipocyte differentiation limited. In this study, we aimed to elucidate changes expression during SDF-1/CXCR7/CXCR4 axis adipogenesis using recombinant ligand CCX771, small interfering RNAs. The results indicated levels SDF-1 receptors, CXCR4, decreased early stages adipogenesis. Treatment with CCX771 inhibited lipid accumulation by inducing β-arrestin2, Wnt expression, AKT phosphorylation downregulating C/EBPα, PPARγ, FABP4 expression. contrast, knockdown preadipocytes downregulated β-arrestin2/Wnt pathway, leading induction Meanwhile, CXCR4 had no significant effect. mice, basal gene were higher stromal vascular fraction compared mature adipocytes significantly upregulated high-fat diet. Our provide new insights into local SDF-1-CXCR7 offer additional benefits prevention obesity-related metabolic disorders.

Language: Английский

Citations

0
Distinguishing the impact of distinct obstructive sleep apnea syndrome (OSAS) and obesity related factors on human monocyte subsets DOI Creative Commons
Ralph Pries,

Friederike Katharina Kosyna,

Reinhard Depping

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Jan. 3, 2024

Abstract Obstructive sleep apnea syndrome (OSAS) and obesity go hand in the majority of patients both are associated with a systemic inflammation, immune disturbance comorbidities such as cardiovascular disease. However, unambiguous impact OSAS on individual inflammatory microenvironment immunological consequences human monocytes has not been distinguished yet. Therefore, aim this study was to investigate related factors by performing flow cytometric whole blood measurements CD14/CD16 monocyte subsets normal weight patients, but without OSAS, obesity, compared healthy donors. Moreover, explicitly plasma levels mediators adiponectin, leptin, lipocalin metalloproteinase-9 were determined influence different cytokine secretion expression adhesion molecules THP-1 analysed. Our data revealed significant redistribution circulating classical intermediate all three patient cohorts, differential effects terms monocytic CD11a, CD11b, CD11c, CX3CR1, CD29, CD49d, levels. These reflected TNFα hypoxia patterns CD11b CD49d. In summary, our which underlines need for customized therapeutic regimen respect weighting these overlapping diseases.

Language: Английский

Citations

3
Lipocalin‐2 induced LDHA expression promotes vascular remodelling in pulmonary hypertension DOI Creative Commons
Guoliang Wang, Shenghua Liu, Xiaohui Kong

et al.

Cell Proliferation, Journal Year: 2024, Volume and Issue: 57(12)

Published: July 18, 2024

Aerobic glycolysis is involved in the pathogenesis of pulmonary hypertension (PH). The mechanisms by which increased and how it contributes to vascular remodelling are not yet fully understood. In this study, we demonstrated that elevated lipocalin-2 (LCN2) PH significantly enhances aerobic human artery smooth muscle cells (PASMCs) up-regulating LDHA expression. Knockout Lcn2 or having heterozygous deficiency mice inhibits progression hypoxic PH. Our study reveals LCN2 stimulates expression activating Akt-HIF-1α signalling pathway. Inhibition Akt HIF-1α reduces proliferation PASMCs. Both play critical roles development suppressed vessels lacking LCN2. These findings shed light on LCN2-Akt-HIF1α-LDHA axis

Language: Английский

Citations

3