ArticleThe Journal of biological chemistry2015
SMAD3 negatively regulates serum irisin and skeletal muscle FNDC5 and peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) during exercise.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 94 citations in OpenAlex.
- Skeletal muscle dysfunction in COPD: miRNAs, myokines and exercise.ERJ open research · 2026Review
- FNDC5/Irisin Attenuates TGF-β-induced Fibroblast Differentiation Via AMPK/Nrf2 Signaling and Mitochondrial Stabilization in Subepithelial Fibrosis.Inflammation · 2026Article
- Deletion of fibro-adipogenic progenitors-specific follistatin impairs muscle function and accelerates skeletal muscle atrophy in obese mice.Molecular medicine (Cambridge, Mass.) · 2025Article
- From Skeletal Muscle to Myocardium: Molecular Mechanisms of Exercise-Induced Irisin Regulation of Cardiac Fibrosis.International journal of molecular sciences · 2025Review
- CCL2 signaling promotes skeletal muscle wasting in non-tumor and breast tumor models.Disease models & mechanisms · 2024Article
- Diabetes Pharmacotherapy and its effects on the Skeletal Muscle Energy Metabolism.Mini reviews in medicinal chemistry · 2024Review
- Irisin deficiency exacerbates diet-induced insulin resistance and cardiac dysfunction in type II diabetes in mice.American journal of physiology. Cell physiology · 2023Article
- Peripheral Regulation of Central Brain-Derived Neurotrophic Factor Expression through the Vagus Nerve.International journal of molecular sciences · 2023Review
- Hypermethylation of the Bmp4 promoter dampens binding of HIF-1α and impairs its cardiac protective effects from oxidative stress in prenatally GC-exposed offspring.Cellular and molecular life sciences : CMLS · 2023Article
- Early-life exercise primes the murine neural epigenome to facilitate gene expression and hippocampal memory consolidation.Communications biology · 2023Article
- Article
- Irisin, an Effective Treatment for Cardiovascular Diseases?Journal of cardiovascular development and disease · 2022Review
- Myostatin/Activin Receptor Ligands in Muscle and the Development Status of Attenuating Drugs.Endocrine reviews · 2022Review
- Dysregulated myokines and signaling pathways in skeletal muscle dysfunction in a cigarette smoke-induced model of chronic obstructive pulmonary disease.Frontiers in physiology · 2022Article
- Irisin, Exercise, and COVID-19.Frontiers in endocrinology · 2022Review
- Serum Levels of Irisin Predict Cumulative Clinical Outcomes in Heart Failure Patients With Type 2 Diabetes Mellitus.Frontiers in physiology · 2022Article
- Article
- Fibronectin type III domain-containing 5 in cardiovascular and metabolic diseases: a promising biomarker and therapeutic target.Acta pharmacologica Sinica · 2021Article
- Progress and Challenges in the Biology of FNDC5 and Irisin.Endocrine reviews · 2021Review
- BDNF Impact on Biological Markers of Depression-Role of Physical Exercise and Training.International journal of environmental research and public health · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Beige adipose cells are a distinct and inducible type of thermogenic fat cell that express the mitochondrial uncoupling protein-1 and thus represent a powerful target for treating obesity. Mice lacking the TGF-β effector protein SMAD3 are protected against diet-induced obesity because of browning of their white adipose tissue (WAT), leading to increased whole body energy expenditure. However, the role SMAD3 plays in WAT browning is not clearly understood. Irisin is an exercise-induced skeletal muscle hormone that induces WAT browning similar to that observed in SMAD3-deficient mice. Together, these observations suggested that SMAD3 may negatively regulate irisin production and/or secretion from skeletal muscle. To address this question, we used wild-type and SMAD3 knock-out (Smad3(-/-)) mice subjected to an exercise regime and C2C12 myotubes treated with TGF-β, a TGF-β receptor 1 pharmacological inhibitor, adenovirus expressing constitutively active SMAD3, or siRNA against SMAD3. We find that in Smad3(-/-) mice, exercise increases serum irisin and skeletal muscle FNDC5 (irisin precursor) and its upstream activator peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) to a greater extent than in wild-type mice. In C2C12 myotubes, TGF-β suppresses FNDC5 and PGC-1α mRNA and protein levels via SMAD3 and promotes SMAD3 binding to the FNDC5 and PGC-1α promoters. These data establish that SMAD3 suppresses FNDC5 and PGC-1α in skeletal muscle cells. These findings shed light on the poorly understood regulation of irisin/FNDC5 by demonstrating a novel association between irisin and SMAD3 signaling in skeletal muscle.
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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.