ArticleBritish journal of pharmacology2016
The role of metformin and resveratrol in the prevention of hypoxia-inducible factor 1α accumulation and fibrosis in hypoxic adipose tissue.
Article in British journal of pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Pooled it
- Hypoxia-Induced Ferroptosis Resistance Drives Orbital Fibrosis in Thyroid Eye Disease.Investigative ophthalmology & visual science · 2026Article
- Pathogenesis of Adenomyosis: An Integrated Review of Cellular Origins, Molecular Mechanisms, and Intersecting Diseases.Journal of cellular and molecular medicine · 2026Review
- New Perspectives on the Use of Resveratrol in the Treatment of Metabolic and Estrogen-Dependent Conditions Through Hormonal Modulation and Anti-Inflammatory Effects.Current issues in molecular biology · 2025Review
- Effects of Resveratrol on Adipocytes: Evidence from In Vitro and In Vivo Studies.Molecules (Basel, Switzerland) · 2024Review
- Red Oranges and Olive Leaf Waste-Derived Bioactive Extracts Promote Adipocyte Functionality In Vitro.Nutrients · 2024Article
- The role of Sirtuin 1 in regulation of fibrotic genes expression in pre-adipocytes.Journal of diabetes and metabolic disorders · 2024Article
- Epicardial Adipose Tissue: a Potential Therapeutic Target for Cardiovascular Diseases.Journal of cardiovascular translational research · 2024Review
- Resveratrol as sensitizer in colorectal cancer plasticity.Cancer metastasis reviews · 2024Review
- Mulberry andFrontiers in endocrinology · 2024Article
- Attenuation of palmitic acid-induced lysyl oxidase overexpression in the ovary contributes to the improvement of ovulation in obesity by metformin.Human reproduction open · 2024Article
- A comparative study of metformin and nicotinamide riboside in alleviating tissue aging in rats.Life medicine · 2023Article
- Gut Microbiota and Aging: Traditional Chinese Medicine and Modern Medicine.Clinical interventions in aging · 2023Review
- Nicotinamide mononucleotide attenuates HIF-1α activation and fibrosis in hypoxic adipose tissueFrontiers in endocrinology · 2023Article
- Resveratrol Regulates Glucose and Lipid Metabolism in Diabetic Rats by Inhibition of PDK1/AKT Phosphorylation and HIF-1α Expression.Diabetes, metabolic syndrome and obesity : targets and therapy · 2023Article
- Mutual Regulation between Redox and Hypoxia-Inducible Factors in Cardiovascular and Renal Complications of Diabetes.Antioxidants (Basel, Switzerland) · 2022Review
- Resveratrol in Treating Diabetes and Its Cardiovascular Complications: A Review of Its Mechanisms of Action.Antioxidants (Basel, Switzerland) · 2022Review
- Standard of care for lipedema in the United States.Phlebology · 2021Article
- Increased Adipose Tissue Fibrogenesis, Not Impaired Expandability, Is Associated With Nonalcoholic Fatty Liver Disease.Hepatology (Baltimore, Md.) · 2021Article
- Metformin and Fibrosis: A Review of Existing Evidence and Mechanisms.Journal of diabetes research · 2021Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeHypoxic activation of hypoxia-inducible factor 1α (HIF-1α) and fibrosis in adipose tissue contribute to adipose dysfunction. This study was designed to investigate the effects of metformin and resveratrol on the regulation of HIF-1α and fibrosis in hypoxic adipose tissue. EXPERIMENTAL APPROACH: Mice were fed a high-fat diet to induce hypoxia and fibrosis in adipose tissue; adipose tissue incubated in vitro in 1% O2 showed a similar change. The effects of metformin and resveratrol on hypoxia, HIF-1α accumulation, endoplasmic reticulum stress and gene expressions of extracellular matrix components and pro-inflammatory cytokines were examined. KEY
resultsOral administration of metformin or resveratrol prevented hypoxia and reduced HIF-1α accumulation with dephosphorylation of inositol-requiring enzyme 1α and eukaryotic initiation factor 2α, indicative of suppression of hypoxic HIF-1α activation and endoplasmic reticulum stress. Metformin and resveratrol down-regulated gene expressions of Col3α, Col6α, elastin and lysyl oxidase and thereby reduced collagen deposition in adipose tissue. The increased gene expressions of TNF-α, IL-6, monocyte chemoattractant protein 1 and F4/80 were also down-regulated by metformin and resveratrol. Metformin and resveratrol had similar effects in adipose tissue exposed to 1% O2 . Metformin reduced ATP production and prevented the reduction in oxygen tension in 3T3-L1 cells, suggesting that it prevented hypoxia by limiting oxygen consumption, whereas resveratrol reduced HIF-1α accumulation by promoting its proteasomal degradation via the regulation of AMPK/SIRT1. CONCLUSION AND IMPLICATIONS: Hypoxia and fibrosis are early causes of adipose dysfunction in obesity. Both metformin and resveratrol effectively inhibited HIF-1α activation-induced fibrosis and inflammation in adipose tissue, although by different mechanisms.
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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.