ArticleJournal of applied physiology (Bethesda, Md. : 1985)2016
Fibroblast growth factor 21 is required for beneficial effects of exercise during chronic high-fat feeding.
Article in Journal of applied physiology (Bethesda, Md. : 1985), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Exercise-Induced Fibroblast Growth Factor-21: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2023Pooled it
- A Randomized Controlled Trial to Determine the Impact of Resistance Training versus Aerobic Training on the Management of FGF-21 and Related Physiological Variables in Obese Men with Type 2 Diabetes Mellitus.Journal of sports science & medicine · 2024Trial
- Divergent effects of resistance and endurance exercise on plasma bile acids, FGF19, and FGF21 in humans.JCI insight · 2018Trial
- Exerkines in precision management of metabolic diseases.Chinese medical journal · 2026Review
- Antagonism of β-klotho signaling by peptide 19 impairs wheel running in male mice and potentiates the cisplatin-induced decrease in wheel running.Frontiers in pharmacology · 2026Article
- The role of FGF21 in the metabolic adjustments required for exercise capacity.Life sciences · 2025Review
- Improvements in Exercise for Alzheimer's Disease: Highlighting FGF21-Induced Cerebrovascular Protection.Neurochemical research · 2025Review
- Exercise as a Therapeutic Strategy for Obesity: Central and Peripheral Mechanisms.Metabolites · 2024Review
- Exerkines and cardiometabolic benefits of exercise: from bench to clinic.EMBO molecular medicine · 2024Review
- Transplantation of committed pre-adipocytes from brown adipose tissue improves whole-body glucose homeostasis.iScience · 2024Article
- Octanoic Acid-Enrichment Diet Improves Endurance Capacity and Reprograms Mitochondrial Biogenesis in Skeletal Muscle of Mice.Nutrients · 2022Article
- Molecular Mechanisms of Exercise and Healthspan.Cells · 2022Review
- Hepatokines as a Molecular Transducer of Exercise.Journal of clinical medicine · 2021Review
- The Roles of FGF21 and ALCAT1 in Aerobic Exercise-Induced Cardioprotection of Postmyocardial Infarction Mice.Oxidative medicine and cellular longevity · 2021Article
- Spinal Cord Injury Reduces Serum Levels of Fibroblast Growth Factor-21 and Impairs Its Signaling Pathways in Liver and Adipose Tissue in Mice.Frontiers in endocrinology · 2021Article
- Advances in Biological Functions and Clinical Studies of FGF21.Diabetes, metabolic syndrome and obesity : targets and therapy · 2021Review
- Skeletal Muscle and Bone - Emerging Targets of Fibroblast Growth Factor-21.Frontiers in physiology · 2021Review
- Metabolic communication during exercise.Nature metabolism · 2020Review
- Glucagon-Receptor Signaling Reverses Hepatic Steatosis Independent of Leptin Receptor Expression.Endocrinology · 2020Article
- Fibroblast Growth Factor 21 and the Adaptive Response to Nutritional Challenges.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Exercise is an effective therapy against the metabolic syndrome. However, the molecular pathways underlying the advantageous effects of exercise are elusive. Glucagon receptor signaling is essential for exercise benefits, and recent evidence indicates that a downstream effector of glucagon, fibroblast growth factor 21 (FGF21), is implicated in this response. Therefore, we tested the hypothesis that FGF21 action is necessary in mediating metabolic effects of exercise. We utilized acute exhaustive treadmill exercise in Wistar rats to identify a putative, concomitant increase in plasma glucagon and FGF21 with the increase in glucose and lactate following exercise. To test the necessity of FGF21 action in the exercise response, we exposed FGF21 congenitally deficient mice (Fgf21(-/-)) and their wild-type (Wt) littermates to chronic high-fat (HF) feeding and inoperable (sedentary) or operable (exercise) voluntary running wheels. Physiological tests were performed to assess the role of FGF21 in the beneficial effect of exercise on glucose metabolism. Wt and Fgf21(-/-) littermates exhibited similar running behavior, and exercise was effective in suppressing weight and fat mass gain and dyslipidemia independently of genotype. However, exercise failed to positively affect hepatic triglyceride content and glucose tolerance in HF diet-fed Fgf21(-/-) mice. Furthermore, Fgf21(-/-) mice exhibited an impaired adaptation to exercise training, including reduced AMP-activated protein kinase activity in skeletal muscle. This study demonstrates that FGF21 action is necessary to achieve the full metabolic benefits of exercise during chronic HF feeding.
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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.