ArticleJCI insight2024
Thrombospondin-1 promotes fibro-adipogenic stromal expansion and contractile dysfunction of the diaphragm in obesity.
Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
6 citing papers in PubMed.
- ITCH-Mediated Ubiquitination and Degradation of THBS1: A Key Mechanism for Enhancing Mitochondrial Biogenesis and Alleviating Mouse Skeletal Muscle Atrophy.Acta physiologica (Oxford, England) · 2026Article
- The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction: A Novel Framework to Explain Pathogenesis and Guide Treatment.Journal of the American College of Cardiology · 2025Review
- From fibro/adipogenic progenitors to adipocytes: Understanding adipogenesis in muscle degeneration for disease modulation.The Journal of physiology · 2025Review
- Article
- Obesity and the Importance of Breathing.Cureus · 2025Review
- Uncovering biomarkers and molecular pathways linking NAFLD and AIS: Insights from bioinformatic analysis and experiment.PloS one · 2025Article
Corrections and comments
- Update of
Authors and funding
10 authors.
Funding
Abstract
Pulmonary disorders affect 40%-80% of individuals with obesity. Respiratory muscle dysfunction is linked to these conditions; however, its pathophysiology remains largely undefined. Mice subjected to diet-induced obesity (DIO) develop diaphragm muscle weakness. Increased intradiaphragmatic adiposity and extracellular matrix (ECM) content correlate with reductions in contractile force. Thrombospondin-1 (THBS1) is an obesity-associated matricellular protein linked with muscular damage in genetic myopathies. THBS1 induces proliferation of fibro-adipogenic progenitors (FAPs) - mesenchymal cells that differentiate into adipocytes and fibroblasts. We hypothesized that THBS1 drives FAP-mediated diaphragm remodeling and contractile dysfunction in DIO. We tested this by comparing the effects of dietary challenge on diaphragms of wild-type (WT) and Thbs1-knockout (Thbs1-/-) mice. Bulk and single-cell transcriptomics demonstrated DIO-induced stromal expansion in WT diaphragms. Diaphragm FAPs displayed upregulation of ECM and TGF-β-related expression signatures and augmentation of a Thy1-expressing subpopulation previously linked to type 2 diabetes. Despite similar weight gain, Thbs1-/- mice were protected from these transcriptomic changes and from obesity-induced increases in diaphragm adiposity and ECM deposition. Unlike WT controls, Thbs1-/- diaphragms maintained normal contractile force and motion after DIO challenge. THBS1 is therefore a necessary mediator of diaphragm stromal remodeling and contractile dysfunction in overnutrition and a potential therapeutic target in obesity-associated respiratory dysfunction.
Indexed as
Identifiers
What OpenQuestion holds
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.