ArticleEBioMedicine2020
Obesity-related hypoxia via miR-128 decreases insulin-receptor expression in human and mouse adipose tissue promoting systemic insulin resistance.
Article in EBioMedicine, 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 49 papers.
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Who cites it
49 citing papers in PubMed, 85 citations in OpenAlex.
- Trial
- The Serpin Superfamily in Adipose Tissue Remodeling: Molecular Drivers of Immune-Metabolic Crosstalk and Insulin Sensitivity.Biology · 2026Review
- miR-128-3p and miR-223-3p as Potential Biomarkers of Metabolic Dysfunction in Liver Tissue from Patients Undergoing Metabolic Bariatric Surgery.Obesity surgery · 2026Article
- 3D Bioprinted Fat-Myocardium Model Unravels the Role of Adipocyte Hypertrophy in Atrial Dysfunction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Estrogen and obesity synergistically suppress protein S via HIF1α, enhancing thrombosis potential.The Journal of clinical investigation · 2025Article
- Predicting accelerated fetal growth in pregnancy: beyond maternal hyperglycemia - The role of prothymosin-α, inflammatory cytokines, and angiogenic factors.Journal of clinical & translational endocrinology · 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
- MicroRNA-microbiota interactions: Emerging strategies for modulating intestinal homeostasis and enhancing host health.iMetaOmics · 2025Review
- Association between the new TyG indicator-TyHGB and gestational diabetes mellitus: results from the case-control and prospective cohort studies.Journal of translational medicine · 2025Article
- Article
- Hypoxia in Human Obesity: New Insights from Inflammation towards Insulin Resistance-A Narrative Review.International journal of molecular sciences · 2024Review
- Article
- Therapeutic Impact of Aerobic Exercise on Adolescents with Obesity and Its Association with Expression of miRNAs and Cytokines: A Clinical Approach.Medicina (Kaunas, Lithuania) · 2024Article
- Oxidative Stress, Inflammation, and Mitochondrial Dysfunction: A Link between Obesity and Atrial Fibrillation.Antioxidants (Basel, Switzerland) · 2024Review
- Impact of Aging and a High-Fat Diet on Adipose-Tissue-Derived Extracellular Vesicle miRNA Profiles in Mice.Biomedicines · 2024Article
- Dopamine D2 receptor antagonist counteracts hyperglycemia and insulin resistance in diet-induced obese male mice.PloS one · 2024Article
- Editorial: Transcriptional regulation of glucose metabolism: gaps and controversies, volume II.Frontiers in endocrinology · 2024Article
- Fat Biology in Triple-Negative Breast Cancer: Immune Regulation, Fibrosis, and Senescence.Journal of obesity & metabolic syndrome · 2023Review
- Metformin in Gestational Diabetes Mellitus: To Use or Not to Use, That Is the Question.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Biomarkers of obesity-mediated insulin resistance: focus on microRNAs.Diabetology & metabolic syndrome · 2023Review
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundInsulin resistance in visceral adipose tissue (VAT), skeletal muscle and liver is a prominent feature of most patients with obesity. How this association arises remains poorly understood. The objective of this study was to demonstrate that the decrease in insulin receptor (INSR) expression and insulin signaling in VAT from obese individuals is an early molecular manifestation that might play a crucial role in the cascade of events leading to systemic insulin resistance.
methodsTo clarify the role of INSR and insulin signaling in adipose tissue dysfunction in obesity, we first measured INSR expression in VAT samples from normal-weight subjects and patients with different degrees of obesity. We complemented these studies with experiments on high-fat diet (HFD)-induced obese mice, and in human and murine adipocyte cultures, in both normoxic and hypoxic conditions.
findingsAn inverse correlation was observed between increasing body mass index and decreasing INSR expression in VAT of obese humans. Our results indicate that VAT-specific downregulation of INSR is an early event in obesity-related adipose cell dysfunction, which increases systemic insulin resistance in both obese humans and mice. We also provide evidence that obesity-related hypoxia in VAT plays a determinant role in this scenario by decreasing INSR mRNA stability. This decreased stability is through the activation of a miRNA (miR-128) that downregulates INSR expression in adipocytes.
interpretationWe present a novel pathogenic mechanism of reduced INSR expression and insulin signaling in adipocytes. Our data provide a new explanation linking obesity with systemic insulin resistance.
fundingThis work was partly supported by a grant from Nutramed (PON 03PE000_78_1) and by the European Commission (FESR FSE 2014-2020 and Regione Calabria).
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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.