ArticleMolecular metabolism2015
Blockade of VEGF-C and VEGF-D modulates adipose tissue inflammation and improves metabolic parameters under high-fat diet.
Article in Molecular metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 1 of them a synthesis that pooled it.
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Who cites it
71 citing papers in PubMed, 1 synthesis or guideline pooled it, 110 citations in OpenAlex.
- Lipedema: Progress, Challenges, and the Road Ahead.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025Pooled it
- Bidirectional crosstalk between obesity and the lymphatic system: a novel pathway in obesity pathogenesis and treatment.International journal of obesity (2005) · 2026Review
- Dysfunctional adipose tissue-lymphatic crosstalk in obesity.Nature reviews. Endocrinology · 2026Review
- High-fat diet feeding induces organ-specific vascular remodeling with distinct temporal dynamics in male mice.Communications biology · 2026Article
- Podocyte-directed VEGFC gene therapy prevents increased glomerular permeability and glycocalyx damage in experimental type 1 diabetes.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Lymphatic dysfunction and impaired interstitial clearance in sarcopenic obesity: a hypothesis-generating review.Frontiers in endocrinology · 2026Review
- Intergenerational effects of early life protein restriction on adipose tissue development as revealed by sheep transcriptomic analyses.Scientific reports · 2025Article
- sVEGFR3 alleviates myocardial ischemia/reperfusion injury through regulating mitochondrial homeostasis and immune cell infiltration.Apoptosis : an international journal on programmed cell death · 2025Article
- Characterization of the Biological Variability of the Angiome Biomarkers over Time in Healthy Participants.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2025Article
- SIX1 aggravates the progression of spinal cord injury in mice by promoting M1 polarization of microglia.Scientific reports · 2025Article
- Leukocyte-lymphatic intersections during cardiac inflammation.Journal of molecular and cellular cardiology · 2025Review
- Recent advances of myotubularin-related (MTMR) protein family in cardiovascular diseases.Frontiers in cardiovascular medicine · 2024Review
- Central insulin dysregulation in antipsychotic-naïve first-episode psychosis: In silico exploration of gene expression signatures.Psychiatry research · 2024Article
- VEGFR-3 signaling in macrophages: friend or foe in disease?Frontiers in immunology · 2024Review
- The Sympathetic Nervous System Promotes Hepatic Lymphangiogenesis, which Is Protective Against Liver Fibrosis.The American journal of pathology · 2023Article
- [Obesity and secondary lymphedema].Dermatologie (Heidelberg, Germany) · 2023Review
- Large scale phenotype imputation and in vivo functional validation implicate ADAMTS14 as an adiposity gene.Nature communications · 2023Article
- The Role of VEGF Family in Lipid Metabolism.Current pharmaceutical biotechnology · 2023Article
- Global Single-Cell Sequencing Landscape of Adipose Tissue of Different Anatomical Site Origin in Humans.Stem cells international · 2023Article
- Increased adipose tissue lymphatic vessel density inhibits thermogenesis through elevated neurotensin levels.Frontiers in cell and developmental biology · 2023Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
objectiveElevated serum levels of the lymphangiogenic factors VEGF-C and -D have been observed in obese individuals but their relevance for the metabolic syndrome has remained unknown.
methodsK14-VEGFR-3-Ig (sR3) mice that constitutively express soluble-VEGFR-3-Ig in the skin, scavenging VEGF-C and -D, and wildtype (WT) mice were fed either chow or high-fat diet for 20 weeks. To assess the effect of VEGFR-3 blockage on adipose tissue growth and insulin sensitivity, we evaluated weight gain, adipocyte size and hepatic lipid accumulation. These results were complemented with insulin tolerance tests, FACS analysis of adipose tissue macrophages, in vitro 3T3-L1 differentiation assays and in vivo blocking antibody treatment experiments.
resultsWe show here that sR3 mice are protected from obesity-induced insulin resistance and hepatic lipid accumulation. This protection is associated with enhanced subcutaneous adipose tissue hyperplasia and an increased number of alternatively-activated (M2) macrophages in adipose tissue. We also show that VEGF-C and -D are chemotactic for murine macrophages and that this effect is mediated by VEGFR-3, which is upregulated on M1 polarized macrophages. Systemic antibody blockage of VEGFR-3 in db/db mice reduces adipose tissue macrophage infiltration and hepatic lipid accumulation, and improves insulin sensitivity.
conclusionsThese results reveal an unanticipated role of the lymphangiogenic factors VEGF-C and -D in the mediation of metabolic syndrome-associated adipose tissue inflammation. Blockage of these lymphangiogenic factors might constitute a new therapeutic strategy for the prevention of obesity-associated insulin resistance.
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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 OpenQuestion graph.