ArticlePloS one2013
Common genetic variation in the human FNDC5 locus, encoding the novel muscle-derived 'browning' factor irisin, determines insulin sensitivity.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 2 of them syntheses that pooled it.
What it found
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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
42 citing papers in PubMed, 2 syntheses or guidelines pooled it, 103 citations in OpenAlex.
- The Effect of Bariatric Surgery on Irisin Level: a Systematic Review and Meta-analysis.Obesity surgery · 2023Pooled it
- Associations between rs3480 and rs16835198 gene polymorphisms ofFrontiers in endocrinology · 2022Pooled it
- Irisin: Emerging Therapeutic Targets for Cognitive Impairment-Related Diseases.Expert reviews in molecular medicine · 2025Review
- Role and Functions of Irisin: A Perspective on Recent Developments and Neurodegenerative Diseases.Antioxidants (Basel, Switzerland) · 2025Review
- Understanding the Role of Irisin in Longevity and Aging: A Narrative Review.Epidemiologia (Basel, Switzerland) · 2025Review
- Relationship of serum irisin levels, physical activity, and metabolic syndrome biomarkers in obese individuals with low-calorie intake and non-obese individuals with high-calorie intake.Journal of health, population, and nutrition · 2025Article
- Astragaloside IV inhibits angiotensin II-induced atrial fibrosis and atrial fibrillation by SIRT1/PGC-1α/FNDC5 pathway.Heliyon · 2024Article
- Sarcopenia as a Risk Factor for Alzheimer's Disease: Genetic and Epigenetic Perspectives.Genes · 2024Review
- Evaluation of serum levels of Irisin as a marker of endothelial dysfunction in patients with type 2 diabetes mellitus.Endocrinology, diabetes & metabolism · 2023Article
- Association of the fibronectin type III domain-containing protein 5 rs1746661 single nucleotide polymorphism with reduced brain glucose metabolism in elderly humans.Brain communications · 2023Article
- An Association BetweenDiabetes, metabolic syndrome and obesity : targets and therapy · 2023Article
- Review
- What Is the Relationship Between Body Mass Index, Sex Hormones, Leptin, and Irisin in Children and Adolescents? A Path Analysis.Frontiers in pediatrics · 2022Article
- Fibronectin type III domain-containing 5 in cardiovascular and metabolic diseases: a promising biomarker and therapeutic target.Acta pharmacologica Sinica · 2021Article
- Common single nucleotide polymorphisms in the FNDC5 gene and serum irisin levels in acute myocardial infarction.Anatolian journal of cardiology · 2021Article
- Multiple Roles in Neuroprotection for the Exercise Derived Myokine Irisin.Frontiers in aging neuroscience · 2021Review
- Exercise-Induced Myokines can Explain the Importance of Physical Activity in the Elderly: An Overview.Healthcare (Basel, Switzerland) · 2020Review
- A pilot study on the relation between irisin single-nucleotide polymorphism and risk of myocardial infarction.Biochemistry and biophysics reports · 2020Article
- Exercise-Induced Circulating Irisin Level Is Correlated with Improved Cardiac Function in Rats.International journal of environmental research and public health · 2020Article
- Circulating irisin is linked to bone mineral density in geriatric Chinese men.Open medicine (Warsaw, Poland) · 2020Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisRecently, the novel myokine irisin was described to drive adipose tissue 'browning', to increase energy expenditure, and to improve obesity and insulin resistance in high fat-fed mice. Here, we assessed whether common single nucleotide polymorphisms (SNPs) in the FNDC5 locus, encoding the irisin precursor, contribute to human prediabetic phenotypes (overweight, glucose intolerance, insulin resistance, impaired insulin release).
methodsA population of 1,976 individuals was characterized by oral glucose tolerance tests and genotyped for FNDC5 tagging SNPs. Subgroups underwent hyperinsulinaemic-euglycaemic clamps, magnetic resonance imaging/spectroscopy, and intravenous glucose tolerance tests. From 37 young and 14 elderly participants recruited in two different centres, muscle biopsies were obtained for the preparation of human myotube cultures.
resultsAfter appropriate adjustment and Bonferroni correction for the number of tested variants, SNPs rs16835198 and rs726344 were associated with in vivo measures of insulin sensitivity. Via interrogation of publicly available data from the Meta-Analyses of Glucose and Insulin-related traits Consortium, rs726344's effect on insulin sensitivity was replicated. Moreover, novel data from human myotubes revealed a negative association between FNDC5 expression and appropriately adjusted in vivo measures of insulin sensitivity in young donors. This finding was replicated in myotubes from elderly men. CONCLUSIONS/
interpretationThis study provides evidence that the FNDC5 gene, encoding the novel myokine irisin, determines insulin sensitivity in humans. Our gene expression data point to an unexpected insulin-desensitizing effect of irisin.
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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 Socratic graph.