ArticleArteriosclerosis, thrombosis, and vascular biology2015
Forkhead box O-1 modulation improves endothelial insulin resistance in human obesity.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 38 citations in OpenAlex.
- Obesity drives depot-specific vascular remodeling in male white adipose tissue.Nature communications · 2025Article
- Exogenous Nucleotides Ameliorate Insulin Resistance Induced by Palmitic Acid in HepG2 Cells through the IRS-1/AKT/FOXO1 Pathways.Nutrients · 2024Article
- Blood-brain barrier genetic disruption leads to protective barrier formation at the Glia Limitans.PLoS biology · 2020Article
- Article
- FSP27 and Links to Obesity and Diabetes Mellitus.Current obesity reports · 2019Review
- Fat-Specific Protein 27 Regulation of Vascular Function in Human Obesity.Journal of the American Heart Association · 2019Article
- Oxidative modifications of mitochondrial complex II are associated with insulin resistance of visceral fat in obesity.American journal of physiology. Endocrinology and metabolism · 2019Article
- Article
- Assessment of Human Adipose Tissue Microvascular Function Using Videomicroscopy.Journal of visualized experiments : JoVE · 2017Article
- Metabolic Regulation of Angiogenesis in Diabetes and Aging.Physiology (Bethesda, Md.) · 2017Review
- WNT5A regulates adipose tissue angiogenesis via antiangiogenic VEGF-AAmerican journal of physiology. Heart and circulatory physiology · 2017Article
- WNT5A-JNK regulation of vascular insulin resistance in human obesity.Vascular medicine (London, England) · 2016Article
- Impact of Diabetes Mellitus.Arteriosclerosis, thrombosis, and vascular biology · 2016Review
- Obesity-Induced Changes in Adipose Tissue Microenvironment and Their Impact on Cardiovascular Disease.Circulation research · 2016Review
- Ageing, metabolism and cardiovascular disease.The Journal of physiology · 2016Review
- MicroRNA-181b Improves Glucose Homeostasis and Insulin Sensitivity by Regulating Endothelial Function in White Adipose Tissue.Circulation research · 2016Article
- Effect of Bariatric Weight Loss on the Adipose Lipolytic Transcriptome in Obese Humans.Mediators of inflammation · 2015Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveIncreased visceral adiposity has been closely linked to insulin resistance, endothelial dysfunction, and cardiometabolic disease in obesity, but pathophysiological mechanisms are poorly understood. We sought to investigate mechanisms of vascular insulin resistance by characterizing depot-specific insulin responses and gain evidence that altered functionality of transcription factor forkhead box O-1 (FOXO-1) may play an important role in obesity-related endothelial dysfunction. APPROACH AND
resultsWe intraoperatively collected paired subcutaneous and visceral adipose tissue samples from 56 severely obese (body mass index, 43 ± 7 kg/m(2)) and 14 nonobese subjects during planned surgical operations, and characterized depot-specific insulin-mediated responses using Western blot and quantitative immunofluorescence techniques. Insulin signaling via phosphorylation of FOXO-1 and consequent endothelial nitric oxide synthase stimulation was selectively impaired in the visceral compared with subcutaneous adipose tissue and endothelial cells of obese subjects. In contrast, tissue actions of insulin were preserved in nonobese individuals. Pharmacological antagonism with AS1842856 and biological silencing using small interfering RNA-mediated FOXO-1 knockdown reversed insulin resistance and restored endothelial nitric oxide synthase activation in the obese.
conclusionsWe observed profound endothelial insulin resistance in the visceral adipose tissue of obese humans which improved with FOXO-1 inhibition. FOXO-1 modulation may represent a novel therapeutic target to diminish vascular insulin resistance. In addition, characterization of endothelial insulin resistance in the adipose microenvironment may provide clues to mechanisms of systemic disease in human obesity.
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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 Socratic graph.