ArticleCirculation2020
Suppression of Endothelial AGO1 Promotes Adipose Tissue Browning and Improves Metabolic Dysfunction.
Article in Circulation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 59 citations in OpenAlex.
- Cross-Platform Analysis of Endothelial Transcriptomic Changes Associated with Diabetes.Research square · 2026Article
- Endothelial AGO1 deficiency reduces breast cancer burden in mice.Angiogenesis · 2026Article
- Single-Cell Metabolic Imaging Reveals Glycogen-Driven Adaptations in Endothelial Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Endothelial IRE1α promotes thrombospondin-1 mRNA decay and supports metabolic stress adaptation of pancreatic islets.Nature communications · 2026Article
- Endothelial dysfunction and cardiovascular outcomes in pre-menopausal women with high vs low breast fat accumulation: The role of TSP-1.American journal of preventive cardiology · 2025Article
- Interleukin 33 Promotes Liver Sinusoidal Endothelial Cell Dysfunction and Hepatic Fibrosis in Diabetic Mice.Diabetes & metabolism journal · 2025Article
- Circulating Thrombospondin-1 and Endothelin-1 Levels Tend to Decline with Increasing Obesity Severity in Women: Evidence from a Pilot, Cross-Sectional Study.Journal of clinical medicine · 2025Article
- Endothelial SIRT3 deficiency predisposes brown adipose tissue to whitening in diet-induced obesity.International journal of biological sciences · 2025Article
- Endothelial Dysfunction in the Tubule Area Accelerates the Progression of Early Diabetic Kidney Disease.Physiological research · 2024Article
- Bioinformatics Analysis and Experimental Validation of Differential Genes and Pathways in Bone Nonunions.Biochemical genetics · 2024Article
- Article
- Hypoxia and low-glucose environments co-induced HGDILnc1 promote glycolysis and angiogenesis.Cell death discovery · 2024Article
- Endothelial TET2 regulates the white adipose browning and metabolism via fatty acid oxidation in obesity.Redox biology · 2024Article
- NeuroD1 Regulated Endothelial Gene Expression to Modulate Transduction of AAV-PHP.eB and Recovery Progress after Ischemic Stroke.Aging and disease · 2023Article
- The evolving functions of the vasculature in regulating adipose tissue biology in health and obesity.Nature reviews. Endocrinology · 2023Review
- Article
- Deletion of endothelial leptin receptors in mice promotes diet-induced obesity.Scientific reports · 2023Article
- Genetic Deletion of theNon-coding RNA · 2023Article
- Endotheliopathy in the metabolic syndrome: Mechanisms and clinical implications.Pharmacology & therapeutics · 2023Review
- The preliminary study of exosomes derived from thymosin beta 4-treated adipose-derived stem cells in fat grafting.Genes & genomics · 2023Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundMetabolic disorders such as obesity and diabetes mellitus can cause dysfunction of endothelial cells (ECs) and vascular rarefaction in adipose tissues. However, the modulatory role of ECs in adipose tissue function is not fully understood. Other than vascular endothelial growth factor-vascular endothelial growth factor receptor-mediated angiogenic signaling, little is known about the EC-derived signals in adipose tissue regulation. We previously identified Argonaute 1 (AGO1; a key component of microRNA-induced silencing complex) as a crucial regulator in hypoxia-induced angiogenesis. In this study, we intend to determine the AGO1-mediated EC transcriptome, the functional importance of AGO1-regulated endothelial function in vivo, and the relevance to adipose tissue function and obesity.
methodsWe generated and subjected mice with EC-AGO1 deletion (EC-AGO1-knockout [KO]) and their wild-type littermates to a fast food-mimicking, high-fat high-sucrose diet and profiled the metabolic phenotypes. We used crosslinking immunoprecipitation- and RNA-sequencing to identify the AGO1-mediated mechanisms underlying the observed metabolic phenotype of EC-AGO1-KO. We further leveraged cell cultures and mouse models to validate the functional importance of the identified molecular pathway, for which the translational relevance was explored using human endothelium isolated from healthy donors and donors with obesity/type 2 diabetes mellitus.
resultsWe identified an antiobesity phenotype of EC-AGO1-KO, evident by lower body weight and body fat, improved insulin sensitivity, and enhanced energy expenditure. At the organ level, we observed the most significant phenotype in the subcutaneous and brown adipose tissues of KO mice, with greater vascularity and enhanced browning and thermogenesis. Mechanistically, EC-AGO1 suppression results in inhibition of thrombospondin-1 (
conclusionsOur study suggests a novel mechanism by which ECs, through the AGO1-TSP1 pathway, control vascularization and function of adipose tissues, insulin sensitivity, and whole-body metabolic state.
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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.