ArticleThe Biochemical journal2011
Adiponectin inhibits leptin signalling via multiple mechanisms to exert protective effects against hepatic fibrosis.
Article in The Biochemical journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 90 citations in OpenAlex.
- Role of adipocytes and their derived extracellular vesicles in the progression, diagnosis and treatment of liver diseases (Review).International journal of molecular medicine · 2026Review
- Mineralocorticoid Receptor Antagonists for Liver Fibrosis: Potential Mechanisms and Research Progress.Journal of clinical and translational hepatology · 2026Review
- Hidradenitis suppurativa: epidemiology, diagnosis, molecular pathogenesis and therapy.Molecular biomedicine · 2026Review
- Efimosfermin for the Treatment of Metabolic Dysfunction-Associated Steatohepatitis (MASH): Mechanism of Action, Clinical Development and Emerging Therapeutic Potential.Drug design, development and therapy · 2026Review
- PET microplastics alter the transcriptome profile and oxidative stress markers in the liver of immature piglets: an in vivo study.Archives of toxicology · 2025Article
- Adiponectin deficiency prevents chronic colitis-associated colonic fibrosis via inhibiting CXCL13 production.Journal of advanced research · 2025Article
- The functional role of the extracellular matrix in inflammatory bowel disease associated gut fibrosis.Matrix biology : journal of the International Society for Matrix Biology · 2025Review
- Tirzepatide: a novel therapeutic approach for Alzheimer's disease.Metabolic brain disease · 2025Review
- Tibetan medicine Pa Zhu Wan ameliorates carbon tetrachloride-induced liver fibrosis in rats by regulating the TGF-β-Smad2/3 and IL-6/JAK2/STAT3 signaling pathways.Frontiers in pharmacology · 2025Article
- Naringin from Ganshuang granule inhibits inflammatory to relieve liver fibrosis through TGF-β-Smad signaling pathway.PloS one · 2024Article
- Role of Leptin and Adiponectin in Carcinogenesis.Cancers · 2023Review
- GLP-1 Receptor Agonists in Non-Alcoholic Fatty Liver Disease: Current Evidence and Future Perspectives.International journal of molecular sciences · 2023Review
- The PTP1B Inhibitor Trodusquemine (MSI-1436) Improves Glucose Uptake in Equine Metabolic Syndrome Affected Liver through Anti-Inflammatory and Antifibrotic Activity.International journal of inflammation · 2023Article
- Adiponectin Alleviates Intestinal Fibrosis by Enhancing AMP-Activated Protein Kinase Phosphorylation.Digestive diseases and sciences · 2022Article
- Adiponectin Influences FGF2 in the Developing Porcine Corpus Luteum.Veterinary sciences · 2022Article
- Synthetic adiponectin-receptor agonist, AdipoRon, induces glycolytic dependence in pancreatic cancer cells.Cell death & disease · 2022Article
- Lipophilic Constituents inFrontiers in pharmacology · 2022Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Adiponectin is protective against hepatic fibrosis, whereas leptin promotes fibrosis. In HSCs (hepatic stellate cells), leptin signals via a JAK2 (Janus kinase 2)/STAT3 (signal transducer and activator of transcription 3) pathway, producing effects that enhance ECM (extracellular matrix) deposition. SOCS-3 (suppressor of cytokine signalling-3) and PTP1B (protein tyrosine phosphatase 1B) are both negative regulators of JAK/STAT signalling, and recent studies have demonstrated a role for adiponectin in regulating SOCS-3 expression. In the present study we investigate mechanisms whereby adiponectin dampens leptin signalling and prevents excess ECM production. We treated culture-activated rat HSCs with recombinant adiponectin, leptin, both or neither, and also treated adiponectin knockout (Ad-/-) and wild-type mice with leptin and/or carbon tetrachloride (CCl4) or saline. We analyse JAK2 and Ob-Rb (long form of the leptin receptor) phosphorylation, and PTP1B expression and activity. We also explore potential mechanisms through which adiponectin regulates SOCS-3-Ob-Rb association. Adiponectin inhibits leptin-stimulated JAK2 activation and Ob-Rb phosphorylation in HSCs, whereas both were increased in Ad-/- mice. Adiponectin stimulates PTP1B expression and activity in vitro, whereas PTP1B expression was lower in Ad-/-mice than in wild-type mice. Adiponectin also promotes SOCS-3-Ob-R association and blocks leptin-stimulated formation of extracellular TIMP-1 (tissue inhibitor of metalloproteinases-1)-MMP-1 (matrix metalloproteinase-1) complexes in vitro. These results suggest two novel mechanisms whereby adiponectin inhibits hepatic fibrosis: (i) by promoting binding of SOCS-3 to Ob-Rb, and (ii) by stimulating PTP1B expression and activity, thus inhibiting JAK2/STAT3 signalling at multiple points.
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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.