The DOI matches its Crossref record; 59 of the 59 references it cites were found in a registry or an index.
FGF21 and Cardiac Physiopathology
Open accessAbstract
The heart is not traditionally considered either a target or a site of fibroblast growth factor-21 (FGF21) production. However, recent findings indicate that FGF21 can act as a cardiomyokine; that is, it is produced by cardiac cells at significant levels and acts in an autocrine manner on the heart itself. The heart is sensitive to the effects of FGF21, both systemic and locally generated, owing to the expression in cardiomyocytes of β-Klotho, the key co-receptor known to confer specific responsiveness to FGF21 action. FGF21 has been demonstrated to protect against cardiac hypertrophy, cardiac inflammation, and oxidative stress. FGF21 expression in the heart is induced in response to cardiac insults, such as experimental cardiac hypertrophy and myocardial infarction in rodents, as well as in failing human hearts. Intracellular mechanisms involving PPARα and Sirt1 mediate transcriptional regulation of the FGF21 gene in response to exogenous stimuli. In humans, circulating FGF21 levels are elevated in coronary heart disease and atherosclerosis, and are associated with a higher risk of cardiovascular events in patients with type 2 diabetes. These findings provide new insights into the role of FGF21 in the heart and may offer potential therapeutic strategies for cardiac disease.
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“administration of FGF21 is actually cardioprotective in numerous rodent models93–95.”
From Metabolic messengers: FGF21 (2021) · cites this paper as [93]
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Cites
FGF-21 as a novel metabolic regulator
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“Several lines of evidence indicate that communication among cardiac cells via secreted factors may contribute to myocardial hypertrophic remodeling (55, 56).”
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“FGF21 expression is under the control of peroxisome proliferator-activated receptor-α (PPARα), and the main site of its production and release into the blood is considered to be the liver (1, 3).”
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“FGF21 also has autocrine/paracrine effects, such as induction of hepatic ketogenesis (1).”
BackgroundFGF21 regulates PGC-1α and browning of white adipose tissues in adaptive thermogenesis
Fisher, F. M., Kleiner, S., Douris, N., Fox, E. C., Mepani, R. J., Verdeguer, F., Wu, J., Kharitonenkov, A., Flier, J. S., Maratos-Flier, E., et al. (2012) · Genes & Development · doi:10.1101/gad.177857.111 · Cited by 1,478 · cited 1×
“Endocrine actions of FGF21 include the promotion of glucose uptake by white adipocytes through induction of the glucose transporter, Glut1 (7), activation of brown fat thermogenic activity (8), and promotion of the appearance of brown fat-like cells in white fat – the so-called “browning” process (9).”
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“This transcriptional pathway, which is also known to be involved in the regulation of FGF21 expression in the liver in the context of the control of carbohydrate and lipid metabolism (35), was found to play a pivotal role in controlling FGF21 expression and release in cardiac cells.”
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“As previously mentioned, serum levels of FGF21 are elevated in subjects with adverse lipid profiles, obesity, metabolic syndrome, impaired glucose tolerance, type 2 diabetes mellitus, and hypertension (47, 48).”
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“In this context, transgenic mice with cardiac-specific FGF21 overexpression show increased circulating FGF21 levels and altered body mass composition (26), suggesting that FGF21 released by the heart has the potential to act at a distance in an endocrine manner.”
BackgroundResultInfluentialObesity Is a Fibroblast Growth Factor 21 (FGF21)-Resistant State
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Inflammatory and Non-Inflammatory Risk Factors in Acquired Aortic Valve Stenosis. Doctoral Thesis
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ГОРМОНИ СЕРЦЯ: БІОМЕДИЧНІ ДОСЛІДЖЕННЯ ДИСТАНТНИХ, ПАРАКРИННИХ І АУТОКРИННИХ ВЗАЄМОДІЙ
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Investigating emerging biomarkers for evaluating cardiac insufficiency
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“[28,29] In the context of endocarditis, FGF21 may mitigate the excessive inflammatory response and oxidative stress that contribute to valvular damage and complications.”
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Liver-derived FGF21 contributes to protection against Alzheimer’s disease pathogenesis
Al‐Lahham, R., Dweik, Q., Murthy, S. G. S. S., Gill, S. K., Krishnan, B., Valdebenito, S., Eugenín, E. A., & Elferink, C. J. (2026) · NeuroImmune Pharmacology and Therapeutics · doi:10.1515/nipt-2026-0020
“On the other hand, administration of FGF21 has been linked to cardioprotective effects such as protection against hypertrophy, inflammation, and oxidative stress [83–85].”
Metadata
- Authors
- Planavila, A., Redondo-Angulo, I., & Villarroya, F.
- Affiliations
- Instituto de Salud Carlos III (ES)
- Corresponding author
- Villarroya, Francesc
- Venue
- Frontiers in Endocrinology
- Publisher
- Frontiers Media SA
- Published
- 2015-08-31
- Volume
- 6
- Pages
- 133-133
- ISSN
- 1664-2392 (ISSN-L)
- PMC
- PMC4553397
- OpenAlex
- W1800862889
- Cited by
- 123
- References
- 59
- Citations by year
- 2026: 10 · 2025: 11 · 2024: 8 · 2023: 16 · 2022: 21 · 2021: 21 · 2020: 5 · 2019: 10 · 2018: 3 · 2017: 10 · 2016: 8
- FWCI
- 0.68
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Endocrinology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RECERCAT (Consorci de Serveis Universitaris de Catalunya) (publishedVersion, other-oa)
- Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Fundación BBVA
- European Commission (277713)
- Generalitat de Catalunya (2014SGR-141, 2014SGR)
- Eusko Jaurlaritza
- Banco Bilbao Vizcaya Argentaria
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › GDF15 and Related Biomarkers
- Keywords
- FGF21, β-Klotho, cardiac hypertrophy, myocardial infarction, cardiac inflammation, oxidative stress, PPARα, SIRT1, coronary artery disease, atherosclerosis, type 2 diabetes, heart failure, cardiovascular risk
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