ArticleDiabetes2022
MicroRNA-29 Ameliorates Fibro-Inflammation and Insulin Resistance in HIF1α-Deficient Obese Adipose Tissue by Inhibiting Endotrophin Generation.
Article in Diabetes, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 35 citations in OpenAlex.
- A distinct form of fat fibrosis is linked to insulin resistance in people with HIV.JCI insight · 2026Observational
- Type 2 Diabetes-Induced Molecular and Functional Impairment of Adipose Tissue-Derived Mesenchymal Stromal Cells (ASCs) and Interferon Gamma Priming for Enhanced Diabetic ASC-Based Therapy.Stem cell reviews and reports · 2026Article
- An update on the landscape of collagen bioactive fragments.The FEBS journal · 2026Review
- Targeting COL6A3-C5 with nigericin suppresses endotrophin formation and enhances insulin sensitivity in obesity.Experimental & molecular medicine · 2026Article
- From bench to bedside: adipose tissue fibrosis in obesity, anti-diabetic therapies, and bariatric surgery.The Korean journal of internal medicine · 2026Review
- Immunometabolism in obesity: Understanding the beneficial and detrimental roles of inflammation.PLoS biology · 2026Article
- ETP-specific-knockout mice reveal endotrophin as a key regulator of kidney fibrosis in ischemia-reperfusion injury models.Experimental & molecular medicine · 2025Article
- Cross-platform proteomics signatures of extreme old age.GeroScience · 2025Article
- Integrative proteogenomic analysis identifies COL6A3-derived endotrophin as a mediator of the effect of obesity on coronary artery disease.Nature genetics · 2025Article
- Integrative analysis of candidate MicroRNAs and gene targets for OSA management using in silico and in-vitro approach.Biotechnology notes (Amsterdam, Netherlands) · 2025Article
- Effect of short-term intensive insulin pump therapy on serum endotrophin levels in patients with newly diagnosed type 2 diabetes.Frontiers in endocrinology · 2025Article
- Genome-wide association study reveals candidate genes for litter size and function validation ofFrontiers in veterinary science · 2025Article
- Human miR-1 Stimulates Metabolic and Thermogenic-Related Genes in Adipocytes.International journal of molecular sciences · 2024Article
- Article
- Endotrophin, a Key Marker and Driver for Fibroinflammatory Disease.Endocrine reviews · 2024Review
- Cross-platform proteomics signatures of extreme old age.bioRxiv : the preprint server for biology · 2024Article
- Cardiometabolic characteristics of people with metabolically healthy and unhealthy obesity.Cell metabolism · 2024Article
- PDGFRβ + cell HIF2α is dispensable for white adipose tissue metabolic remodeling and hepatic lipid accumulation in obese mice.Lipids in health and disease · 2024Article
- The Mechanism for Adipose Endotrophin Production.Diabetes · 2022Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dysregulation of extracellular matrix proteins in obese adipose tissue (AT) induces systemic insulin resistance. The metabolic roles of type VI collagen and its cleavage peptide endotrophin in obese AT are well established. However, the mechanisms regulating endotrophin generation remain elusive. Herein, we identified that several endotrophin-containing peptides (pre-endotrophins) were generated from the COL6A3 chain in a stepwise manner for the efficient production of mature endotrophin, partly through the action of hypoxia-induced matrix metalloproteinases (MMPs), including MMP2, MMP9, and MMP16. Hypoxia is an upstream regulator of COL6A3 expression and the proteolytic processing that regulates endotrophin generation. Hypoxia-inducible factor 1α (HIF1α) and the hypoxia-associated suppression of microRNA-29 (miR-29) cooperatively control the levels of COL6A3 and MMPs, which are responsible for endotrophin generation in hypoxic ATs. Adipocyte-specific Hif1α knock-out (APN-HIF1αKO) mice fed a chronic high-fat diet exhibited the significant amelioration of both local fibro-inflammation in AT and systemic insulin resistance compared with their control littermates, partly through the inhibition of endotrophin generation. Strikingly, adenovirus-mediated miR-29 overexpression in the ATs of APN-HIF1αKO mice in obesity significantly decreased endotrophin levels, suggesting that miR-29, combined with HIF1α inhibition in AT, could be a promising therapeutic strategy for treating obesity and related metabolic diseases.
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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.