ArticleMolecular medicine (Cambridge, Mass.)2023
Leptin/obR signaling exacerbates obesity-related neutrophilic airway inflammation through inflammatory M1 macrophages.
Article in Molecular medicine (Cambridge, Mass.), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Phagocytic aberrations in macrophages in asthma: a mechanistic systematic review integratingFrontiers in immunology · 2026Pooled it
- Adipokines as Regulators of Nitric Oxide Synthase Isoforms Across Organs: Emerging Implications for Gastrointestinal Motility.International journal of molecular sciences · 2026Review
- Mechanisms and therapeutic strategies of asthma: from bench to bedside.Signal transduction and targeted therapy · 2026Review
- Causal Inference in Non-Allergic Asthma Associated with Obesity: Application of the Bradford Hill Viewpoints to a Complex Epidemiological Association.Epidemiologia (Basel, Switzerland) · 2026Review
- Targeting CD3L1-NRP2 disarms myeloid-driven tumor immune evasion.EMBO molecular medicine · 2026Article
- Leptin-induced autophagy regulates the immunomodulatory potential of adipose-derived mesenchymal stem cells through down regulating the expression of TSG-6.Scientific reports · 2026Article
- Neutrophilic asthma: advances in experimental models from pathogenesis to therapeutic translation.Molecular medicine (Cambridge, Mass.) · 2026Review
- LEP Knockdown Improves Functional Recovery After Spinal Cord Injury and Potentially Regulates Microglial Polarization via JAK-STAT Signaling Pathway.Neuromolecular medicine · 2026Article
- A Body Shape Index and asthma prevalence in Chinese middle-aged and older adults: a cross-sectional study.BMC pulmonary medicine · 2026Article
- Sophocarpine Alleviates Airway Epithelial Cell Inflammation in Asthma via Modulating the Cytokine- Cytokine Receptor and JAK2/STAT3 Signaling Pathways.Drug design, development and therapy · 2026Article
- Inflammatory Dysregulation, Asthma, and Obesity in Children: What is the Relationship?Journal of inflammation research · 2026Review
- Obesity-associated inflammation and cancer: molecular mechanisms, evidence gaps, and therapeutic opportunities.Frontiers in immunology · 2026Review
- The IDO1/AhR-HIF-1α metabolic axis: ARNT competition as a central antagonistic switch in autoimmune pathogenesis.Frontiers in immunology · 2026Review
- Leptin as a Potential Modifier of Neuroinflammation: Contrasting Roles in Alzheimer's Disease and Multiple Sclerosis.International journal of molecular sciences · 2025Review
- Effect of metformin on airway inflammation in obese asthmatic mice and study of the mechanism involved.Scientific reports · 2025Article
- Review
- Relationship between body mass index, gray matter volume and peripheral inflammation in patients with post-COVID condition.Brain, behavior, & immunity - health · 2025Article
- Research Progress on Leptin in Metabolic Dysfunction-associated Fatty Liver Disease.Journal of clinical and translational hepatology · 2025Review
- Anthocyanins Modulation of Gut Microbiota to Reverse Obesity-Driven Inflammation and Insulin Resistance.Nutrients · 2025Review
- Multi-target Effects of Short-Chain Fatty Acids for Obesity-Related Asthma: Interventional Potential and Challenges.Clinical reviews in allergy & immunology · 2025Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundObesity-related asthma is a kind of nonallergic asthma with excessive neutrophil infiltration in the airways. However, the underlying mechanisms have been poorly elucidated. Among the adipokines related to obesity, leptin is related to the inflammatory response. However, little is understood about how leptin acts on the leptin receptor (obR) in neutrophilic airway inflammation in obesity-associated asthma. We explored the inflammatory effects of leptin/obR signaling in an obesity-related neutrophilic airway inflammation mouse model.
methodsWe established a neutrophilic airway inflammation mouse model using lipopolysaccharide (LPS)/ovalbumin (OVA) sensitization and OVA challenge (LPS + OVA/OVA) in lean, obese, or db/db (obR deficiency) female mice. Histopathological, bronchoalveolar lavage fluid (BALF) inflammatory cell, and lung inflammatory cytokine analyses were used to analyze airway inflammation severity. Western blotting, flow cytometry, reverse transcription-polymerase chain reaction (RT-PCR), and enzyme-linked immunosorbent assay (ELISA) were used to evaluate the underlying mechanisms. In vitro bone marrow-derived macrophage (BMDM) and bone marrow-derived neutrophil experiments were performed.
resultsWe found that the serum leptin level was higher in obese than in lean female mice. Compared to LPS/OVA + OVA-treated lean female mice, LPS/OVA + OVA-treated obese female mice had higher peribronchial inflammation levels, neutrophil counts, Th1/Th17-related inflammatory cytokine levels, M1 macrophage polarization levels, and long isoform obR activation, which could be decreased by the obR blockade (Allo-Aca) or obR deficiency, suggesting a critical role of leptin/obR signaling in the pathogenesis of obesity-related neutrophilic airway inflammation in female mice. In in vitro experiments, leptin synergized with LPS/IFN-γ to promote the phosphorylation of the long isoform obR and JNK/STAT3/AKT signaling pathway members to increase M1 macrophage polarization, which was reversed by Allo-Aca. Moreover, leptin/obR-mediated M1 macrophage activity significantly elevated CXCL2 production and neutrophil recruitment by regulating the JNK/STAT3/AKT pathways. In clinical studies, obese patients with asthma had higher serum leptin levels and M1 macrophage polarization levels in induced sputum than non-obese patients with asthma. Serum leptin levels were positively correlated with M1 macrophage polarization levels in patients with asthma.
conclusionsOur results demonstrate leptin/obR signaling plays an important role in the pathogenesis of obesity-related neutrophilic airway inflammation in females by promoting M1 macrophage polarization.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.