Trial reportCell metabolism2014
Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans.
Trial report in Cell metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02725879 (Association of Serum Fibroblast Growth Factor 21), which is not on this map. Cited by 416 papers, 4 of them syntheses that pooled it.
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.
Association of Serum Fibroblast Growth Factor 21 (FGF-21) Levels With Resting Metabolic Rate (RMR), in Children and Adolescents With Hashimoto's Thyroiditis.
Who cites it
416 citing papers in PubMed, 4 syntheses or guidelines pooled it, 794 citations in OpenAlex.
- Effects of Different Training Modalities on Circulating Irisin Levels in Overweight and Obesity Adults: A Systematic Review and Meta-analysis of Randomized Controlled Trials.Sports medicine (Auckland, N.Z.) · 2026Pooled it
- Research hotspots of irisin in the nervous system: a bibliometric study and visualization analysis via CiteSpace.Frontiers in aging neuroscience · 2025Pooled it
- A Systematic Review and Meta-Analysis of Free Triiodothyronine (FT3) Levels in Humans Depending on Seasonal Air Temperature Changes: Is the Variation in FT3 Levels Related to Nonshivering Thermogenesis?International journal of molecular sciences · 2023Pooled it
- Effect of Chronic Resistance Training on Circulating Irisin: Systematic Review and Meta-Analysis of Randomized Controlled Trials.International journal of environmental research and public health · 2021Pooled it
- Effects of Tabata-style functional training and cinnamon supplementation on army combat fitness test performance, serum irisin, and body composition in military cadets: a randomized controlled trial.Journal of the International Society of Sports Nutrition · 2026Trial
- Fructose-induced FGF21 secretion does not activate brown adipose tissue in Japanese young men: randomized cross-over and randomized controlled trials.Journal of physiological anthropology · 2024Trial
- The Effect of Two Somatic-Based Practices Dance and Martial Arts on Irisin, BDNF Levels and Cognitive and Physical Fitness in Older Adults: A Randomized Control Trial.Clinical interventions in aging · 2024Trial
- Contribution of High-Intensity Interval Exercise in the Fasted State to Fat Browning: Potential Roles of Lactate and β-Hydroxybutyrate.Medicine and science in sports and exercise · 2023Trial
- Effects of interleukin-1 antagonism and corticosteroids on fibroblast growth factor-21 in patients with metabolic syndrome.Scientific reports · 2021Trial
- Fluvastatin Reduces Glucose Tolerance in Healthy Young Individuals Independently of Cold Induced BAT Activity.Frontiers in endocrinology · 2021Trial
- Effects of dapagliflozin on the serum levels of fibroblast growth factor 21 and myokines and muscle mass in Japanese patients with type 2 diabetes: A randomized, controlled trial.Journal of diabetes investigation · 2020Trial
- 6 weeks of fartlek-style endurance training does not alter physiological responses to mild cold exposure but attenuates the cold-induced plasma noradrenaline response: A randomized, matched control trial.Journal of clinical & translational endocrinology · 2026Article
- Cold-induced serum amyloid A3 amplifies cAMP-PKA signaling to drive adaptive thermogenesis in brown adipocytes.Journal of physiology and biochemistry · 2026Article
- Skeletal muscle‑derived extracellular vesicles in multi‑organ degenerative disease: Mechanisms and therapeutic delivery perspectives (Review).International journal of molecular medicine · 2026Review
- N-terminal thrombospondin-1 enhances muscle function and tissue-specific metabolic adaptation in response to exercise and cold exposure.Experimental & molecular medicine · 2026Article
- Brown fat protects against hepatic oxidative stress by remodeling the circulating metabolome.Cell metabolism · 2026Article
- Adipocyte-Derived Leptolin Enhances Energy Expenditure and Prevents Obesity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Circulating METRNL, Adipocytokines, and Insulin-Resistance Markers After Repeated Whole-Body Cryotherapy in Women of Different Ages.International journal of molecular sciences · 2026Article
- Exercise mimetics: molecular mechanisms, biological and therapeutic effects.Molecular biomedicine · 2026Review
- WAT-to-BAT communication facilitates the sustained activation of BAT thermogenesis during cold exposure.Cell discovery · 2026Article
356 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
Rediscovery of cold-activated brown adipose tissue (BAT) in humans has boosted research interest in identifying BAT activators for metabolic benefits. Of particular interest are cytokines capable of fat browning. Irisin, derived from FNDC5, is an exercise-induced myokine that drives brown-fat-like thermogenesis in murine white fat. Here we explored whether cold exposure is an afferent signal for irisin secretion in humans and compared it with FGF21, a brown adipokine in rodents. Cold exposure increased circulating irisin and FGF21. We found an induction of irisin secretion proportional to shivering intensity, in magnitude similar to exercise-stimulated secretion. FNDC5 and/or FGF21 treatment upregulated human adipocyte brown fat gene/protein expression and thermogenesis in a depot-specific manner. These results suggest exercise-induced irisin secretion could have evolved from shivering-related muscle contraction, serving to augment brown fat thermogenesis in concert with FGF21. Irisin-mediated muscle-adipose crosstalk may represent a thermogenic, cold-activated endocrine axis that is exploitable in obesity therapeutics development.
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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.