Attenuated fibroblast growth factor 21 response to acute aerobic exercise in obese individuals
Abstract
Background and aim Fibroblast growth factor 21 (FGF21) is positively associated with body mass index, potentially as a compensatory mechanism to mediate obesity related metabolic and inflammatory insult due to chronic low-grade elevations of the pro-inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). Therefore, FGF21 response in obese subjects and the associations with increased pro-inflammatory cytokines, insulin resistance, and energy utilization warrants investigation. Methods and results Twenty four untrained subjects (12 obese and 12 normal-weight) performed 30 min of continuous submaximal aerobic exercise. Following exercise, obese subjects exhibited a blunted FGF21 response to exercise compared to normal-weight subjects as indicated by area-under-the-curves "with respect to increase" (AUCi) analyses (p = 0.005). Furthermore, while exercise-induced plasma FGF21 was not associated with any inflammatory cytokine (IL-6 and TNF-α) response, FGF21 AUCi was positively correlated with glucose AUCi (r = 0.495, p = 0.014), total relative energy expenditure (r = 0.562, p = 0.004), and relative maximal oxygen consumption (VO2max; r = 0.646, p = 0.001) in all subjects. Conclusion Impaired cardiorespiratory fitness may influence the sensitivity of FGF21 response to acute exercise in obese individuals, potentially contributing to the attenuated metabolic response (e.g., glucose) and total exercise energy expenditure. Therefore, exercise training aimed…
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Training status can affect both baseline and exercise-induced myokine levels; individuals with metabolic syndrome exhibit attenuated irisin responses, and failure to distinguish acute and chronic measurement time points may have contributed to contradictory findings.
“Training status can affect both baseline and exercise-induced myokine levels. For instance, individuals with metabolic syndrome have been found to exhibit attenuated irisin responses [19], and failure to distinguish between acute and chronic measurement time points may have contributed to some contradictory findings in the literature [18,42,50,80].”
From Exercise-Induced Myokines in Obesity-Related Metabolic Disorders and Cardiovascular Protection: A Narrative Review (2026) · cites this paper as [80]
Patients with obesity-related insulin resistance have an impaired FGF21 upregulation after exercise.
“Furthermore, patients with obesity-related insulin resistance have an impaired FGF21 upregulation after exercise [156,157].”
Clinical studies in patients with insulin resistant conditions have described dampened upregulation of exercise-induced factors such as FGF21 and follistatin, most likely due to an altered glucagon-to-insulin ratio.
“Clinical studies in patients with insulin resistant conditions have described dampened upregulation of exercise-induced factors, such as FGF21 and follistatin, most likely due to an altered glucagon-to-insulin ratio [156,157,280]”
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- Authors
- Slusher, A. L., Whitehurst, M., Zoeller, R. F., Mock, J. T., Maharaj, M., & Huang, C.-J.
- Affiliations
- Virginia Commonwealth University (US)
- Florida Atlantic University (US)
- Corresponding author
- Slusher, A.L.
- Venue
- Nutrition Metabolism and Cardiovascular Diseases
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 25
- Issue
- 9
- Pages
- 839-845
- ISSN
- 0939-4753 (ISSN-L)
- OpenAlex
- W1739510955
- Cited by
- 50
- References
- 30
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 7 · 2022: 7 · 2021: 3 · 2020: 6 · 2019: 3 · 2018: 3 · 2017: 8 · 2016: 5
- FWCI
- 2.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nutrition Metabolism and Cardiovascular Diseases (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Keywords
- FGF21, obesity, acute aerobic exercise, cardiorespiratory fitness, interleukin-6, TNF-α, insulin resistance, energy expenditure, glucose metabolism, VO2max, cardioprotection
- MeSH terms
- Adolescent, Adult, Blood Glucose, Body Composition, Body Weight, Cardiovascular Diseases, Energy Metabolism, Female, Fibroblast Growth Factors, Humans, Insulin, Insulin Resistance, Male, Obesity, Oxygen Consumption, Tumor Necrosis Factor-alpha, Exercise, Interleukin-6, Body Mass Index, Case-Control Studies, Waist Circumference, Young Adult
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