ArticleArthritis research & therapy2012
The adipokine adiponectin has potent anti-fibrotic effects mediated via adenosine monophosphate-activated protein kinase: novel target for fibrosis therapy.
Article in Arthritis research & therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 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.
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
67 citing papers in PubMed, 1 synthesis or guideline pooled it, 112 citations in OpenAlex.
- Meta-analysis of circulating adiponectin, leptin, and resistin levels in systemic sclerosis.Zeitschrift fur Rheumatologie · 2017Pooled it
- LLF580, an FGF21 Analog, Reduces Triglycerides and Hepatic Fat in Obese Adults With Modest Hypertriglyceridemia.The Journal of clinical endocrinology and metabolism · 2022Trial
- Bone Marrow Mesenchymal Stromal Cell Treatment in Patients with Osteoarthritis Results in Overall Improvement in Pain and Symptoms and Reduces Synovial Inflammation.Stem cells translational medicine · 2019Trial
- Pegbelfermin (BMS-986036), PEGylated FGF21, in Patients with Obesity and Type 2 Diabetes: Results from a Randomized Phase 2 Study.Obesity (Silver Spring, Md.) · 2019Trial
- A phase 2 randomized dose-ranging study of the JAK2-selective inhibitor fedratinib (SAR302503) in patients with myelofibrosis.Blood cancer journal · 2015Trial
- Adipose Tissue Browning in MASLD and Its Molecular Mechanisms and Metabolic Crosstalk.Current obesity reports · 2026Review
- A Circuit of Mechanically Regulated Transcription Factors Balances Regenerative and Fibrotic Memory of Mesenchymal Stromal Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Pulmonary Fibrosis Beyond the Lung: Adipose Tissue as a Systemic Modifier of Fibrotic Remodeling.Diagnostics (Basel, Switzerland) · 2026Review
- Adipokine networks in diabetic kidney disease: mechanistic insights and therapeutic implications.Lipids in health and disease · 2026Review
- Transforming Myofibroblasts Into Lipid-Filled Cells to Treat Dupuytren Disease.The Journal of hand surgery · 2026Article
- Wnt Activation in Mature Dermal Adipocytes Leads to Lipodystrophy and Skin Fibrosis via ATGL-Dependent Lipolysis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- The Role of Adipokines in Spinal Disease: A Narrative Review.JOR spine · 2025Review
- Immunopharmacological potential ofFrontiers in pharmacology · 2025Review
- Effects and Safety of FGF21 Analogs on Glycemic Parameters, Lipid Profiles, and Adiponectin in Overweight and Obese Adults: A Meta-Analysis of Randomized Controlled Trials.International journal of endocrinology · 2025Review
- Critical Analysis of Cytoplasmic Progression of Inflammatory Signaling Suggests Potential Pharmacologic Targets for Wound Healing and Fibrotic Disorders.Biomedicines · 2024Review
- Article
- A mouse model of progressive lung fibrosis with cutaneous involvement induced by a combination of oropharyngeal and osmotic minipump bleomycin delivery.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Tissue fibrosis associated depletion of lipid-filled cells.Experimental dermatology · 2024Review
- Challenges and opportunities in obesity: the role of adipocytes during tissue fibrosis.Frontiers in endocrinology · 2024Review
- Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
introductionFibrosis in scleroderma is associated with collagen deposition and myofibroblast accumulation. Peroxisome proliferator activated receptor gamma (PPAR-γ), a master regulator of adipogenesis, inhibits profibrotic responses induced by transforming growth factor-ß (TGF-β), and its expression is impaired in scleroderma. The roles of adiponectin, a PPAR-γ regulated pleiotropic adipokine, in regulating the response of fibroblasts and in mediating the effects of PPAR-γ are unknown.
methodsRegulation of fibrotic gene expression and TGF-ß signaling by adiponectin and adenosine monophosphate protein-activated (AMP) kinase agonists were examined in normal fibroblasts in monolayer cultures and in three-dimensional skin equivalents. AdipoR1/2 expression on skin fibroblasts was determined by real-time quantitative PCR.
resultsAdiponectin, an adipokine directly regulated by PPAR-γ, acts as a potent anti-fibrotic signal in normal and scleroderma fibroblasts that abrogates the stimulatory effects of diverse fibrotic stimuli and reduces elevated collagen gene expression in scleroderma fibroblasts. Adiponectin responses are mediated via AMP kinase, a fuel-sensing cellular enzyme that is necessary and sufficient for down-regulation of fibrotic genes by blocking canonical Smad signaling. Moreover, we demonstrate that endogenous adiponectin accounts, at least in part, for the anti-fibrotic effects exerted by ligands of PPAR-γ.
conclusionsThese findings reveal a novel link between cellular energy metabolism and extracellular matrix homeostasis converging on AMP kinase. Since the levels of adiponectin as well as its receptor are impaired in scleroderma patients with progressive fibrosis, the present results suggest a potential role for defective adiponectin expression or function in progressive fibrogenesis in scleroderma and other chronic fibrosing conditions. Restoring the adiponectin signaling axis in fibroblasts might, therefore, represent a novel pharmacological approach to controlling fibrosis.
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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.