ArticleNature metabolism2021
Mesenteric lymphatic dysfunction promotes insulin resistance and represents a potential treatment target in obesity.
Article in Nature metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06455878 (The Impact of Dietary Management Applet for Weight Reduction in Obese Heart Failure Patients), which is not on this map. Cited by 63 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
The Impact of Dietary Management Applet for Weight Reduction in Obese Heart Failure Patients: a Multicenter, Single-blind Randomized Controlled Trial
Who cites it
63 citing papers in PubMed, 99 citations in OpenAlex.
- Bidirectional crosstalk between obesity and the lymphatic system: a novel pathway in obesity pathogenesis and treatment.International journal of obesity (2005) · 2026Review
- Review
- Lymphatic Endothelial Cells in Health and Disease.MedComm · 2026Review
- GLP-1 Receptors Are Enriched in the Lymphatic Endothelium and Their Pharmacological Activation With Semaglutide Improves the Pumping Capacity of Lymphatic Vessels.Microcirculation (New York, N.Y. : 1994) · 2026Article
- The expanding role of formulations to enable oral delivery of poorly water-soluble drugs.Nature reviews. Drug discovery · 2026Review
- Dysfunctional adipose tissue-lymphatic crosstalk in obesity.Nature reviews. Endocrinology · 2026Review
- A reduction-sensitive lipophilic dihydroartemisinin prodrug in a self-microemulsifying drug delivery system for treating breast cancer lung metastasis via intestinal lymphatic transport.International journal of pharmaceutics: X · 2026Article
- Mesenteric adipose tissue: from protective gatekeeper to driver of inflammatory bowel disease.Immunometabolism (Cobham, Surrey) · 2026Review
- Lymphatics-on-a-chip microphysiological system: engineering lymphatic structure and functionLab on a chip · 2026Review
- Effect of free fatty acids on TGF-β1 mediated fibrogenesis in hepatic stellate cells.Molecular metabolism · 2026Article
- Lymphatic dysfunction and impaired interstitial clearance in sarcopenic obesity: a hypothesis-generating review.Frontiers in endocrinology · 2026Review
- Capsaicin attenuates high-fat diet-induced impairment of B-cell immunity.SAGE open medicine · 2026Article
- Tertiary lymphoid structures are associated with lower axillary residual nodal burden in breast cancer patients after neoadjuvant chemotherapy.European journal of medical research · 2025Article
- A Lymphatic Perspective on Obesity and Inflammatory Arthritis: New Disease-Modifying Potential in Rheumatology.Journal of clinical medicine · 2025Article
- S1PR1 regulates lymphatic valve development and tertiary lymphoid organ formation in the ileum.The Journal of experimental medicine · 2025Article
- Defective lymphatic vasculature in obesity.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025Review
- Recent advances in targeting COX-2 for cancer therapy: a review.RSC medicinal chemistry · 2025Review
- Aging-induced changes in lymphatic muscle cell transcriptomes are associated with reduced pumping of peripheral collecting lymphatic vessels in mice.Developmental cell · 2025Article
- Transport functions of intestinal lymphatic vessels.Nature reviews. Gastroenterology & hepatology · 2025Review
- Obesity-Associated Conditions Hinder Solute Drainage Function of Engineered Human Lymphatic Vessels.Cellular and molecular bioengineering · 2025Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
23 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Visceral adipose tissue (VAT) encases mesenteric lymphatic vessels and lymph nodes through which lymph is transported from the intestine and mesentery. Whether mesenteric lymphatics contribute to adipose tissue inflammation and metabolism and insulin resistance is unclear. Here we show that obesity is associated with profound and progressive dysfunction of the mesenteric lymphatic system in mice and humans. We find that lymph from mice and humans consuming a high-fat diet (HFD) stimulates lymphatic vessel growth, leading to the formation of highly branched mesenteric lymphatic vessels that 'leak' HFD-lymph into VAT and, thereby, promote insulin resistance. Mesenteric lymphatic dysfunction is regulated by cyclooxygenase (COX)-2 and vascular endothelial growth factor (VEGF)-C-VEGF receptor (R)3 signalling. Lymph-targeted inhibition of COX-2 using a glyceride prodrug approach reverses mesenteric lymphatic dysfunction, visceral obesity and inflammation and restores glycaemic control in mice. Targeting obesity-associated mesenteric lymphatic dysfunction thus represents a potential therapeutic option to treat metabolic disease.
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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.