ArticleDiabetes2015
Noncanonical Wnt signaling promotes obesity-induced adipose tissue inflammation and metabolic dysfunction independent of adipose tissue expansion.
Article in Diabetes, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
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Who cites it
99 citing papers in PubMed, 164 citations in OpenAlex.
- Fibre-Enriched High-Carbohydrate (FEHC) Diet Modulates Inflammation Without Affecting Bone Health in Older Women With Obesity: A Randomised Clinical Trial.Diabetes/metabolism research and reviews · 2025Trial
- Cumulative effects of exercise training and consumption of propolis on managing diabetic dyslipidemia in adult women: a single-blind, randomized, controlled trial with pre-post-intervention assessments.The journal of physiological sciences : JPS · 2023Trial
- Dysregulation of Subcutaneous White Adipose Tissue Inflammatory Environment Modelling in Non-Insulin Resistant Obesity and Responses to Omega-3 Fatty Acids - A Double Blind, Randomised Clinical Trial.Frontiers in immunology · 2022Trial
- Sappanone A exerted promising therapeutic effects in vitiligo through Wnt5a-mediated noncanonical Wnt signaling.Journal of natural medicines · 2026Article
- Systems genetics reveals ITIH5 as a key mediator of adipocyte-Endothelial crosstalk.Molecular metabolism · 2026Article
- Tiki2 restrains Wnt5a/Ror signaling to limit inflammation in acute kidney injury.Communications biology · 2026Article
- Conditional deletion ofFrontiers in cell and developmental biology · 2026Article
- Inflammation in cardiovascular-kidney-metabolic syndrome: key roles and underlying mechanisms-a comprehensive review.Molecular and cellular biochemistry · 2025Review
- Wnt5a-mediated Adipo-Cardiac Interorgan Communication in HFpEF.bioRxiv : the preprint server for biology · 2025Article
- The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction: A Novel Framework to Explain Pathogenesis and Guide Treatment.Journal of the American College of Cardiology · 2025Review
- Translational disease modeling of peripheral blood identifies type 2 diabetes biomarkers predictive of Alzheimer's disease.NPJ systems biology and applications · 2025Article
- Immune Microenvironment Dysregulation: A Contributing Factor to Obesity-Associated Male Infertility.Biomedicines · 2025Review
- Role of Maternal Obesity in Offspring Cardiovascular Development and Congenital Heart Defects.Journal of the American Heart Association · 2025Article
- Understanding the Role of Adipokines in Cardiometabolic Dysfunction: A Review of Current Knowledge.Biomolecules · 2025Review
- Wnt signaling pathways in biology and disease: mechanisms and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Blocking the SIRPα-CD47 axis promotes macrophage phagocytosis of exosomes derived from visceral adipose tissue and improves inflammation and metabolism in mice.Journal of biomedical science · 2025Article
- Chronodisruption enhances inflammatory cytokine release from visceral adipose tissue in obesity.Journal of translational medicine · 2025Article
- Serum levels of Wnt5a in Egyptian women with obesity and their association with toll like receptor 2 Arg753Gln gene polymorphism in a pilot case control study of obesity as a state of metaflammation.Scientific reports · 2025Article
- Atorvastatin exerts a preventive effect against steroid-induced necrosis of the femoral head by modulating Wnt5a release.Archives of toxicology · 2024Article
- Wnt7b acts in concert with Wnt5a to regulate tissue elongation and planar cell polarity via noncanonical Wnt signaling.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
39 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Adipose tissue dysfunction plays a pivotal role in the development of insulin resistance in obese individuals. Cell culture studies and gain-of-function mouse models suggest that canonical Wnt proteins modulate adipose tissue expansion. However, no genetic evidence supports a role for endogenous Wnt proteins in adipose tissue dysfunction, and the role of noncanonical Wnt signaling remains largely unexplored. Here we provide evidence from human, mouse, and cell culture studies showing that Wnt5a-mediated, noncanonical Wnt signaling contributes to obesity-associated metabolic dysfunction by increasing adipose tissue inflammation. Wnt5a expression is significantly upregulated in human visceral fat compared with subcutaneous fat in obese individuals. In obese mice, Wnt5a ablation ameliorates insulin resistance, in parallel with reductions in adipose tissue inflammation. Conversely, Wnt5a overexpression in myeloid cells augments adipose tissue inflammation and leads to greater impairments in glucose homeostasis. Wnt5a ablation or overexpression did not affect fat mass or adipocyte size. Mechanistically, Wnt5a promotes the expression of proinflammatory cytokines by macrophages in a Jun NH2-terminal kinase-dependent manner, leading to defective insulin signaling in adipocytes. Exogenous interleukin-6 administration restores insulin resistance in obese Wnt5a-deficient mice, suggesting a central role for this cytokine in Wnt5a-mediated metabolic dysfunction. Taken together, these results demonstrate that noncanonical Wnt signaling contributes to obesity-induced insulin resistance independent of adipose tissue expansion.
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Registered trials
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 OpenQuestion graph.