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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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Self-citationCirculating FGF21 Is Liver Derived and Enhances Glucose Uptake During Refeeding and Overfeeding
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“Recent findings also underscore the potential role of FGF21 under conditions of mitochondrial dysfunction, with several studies showing that skeletalmuscle is an FGF21-producing tissue inmice (36, 37) and humans (38), and that a mitochondrial respiratory chain deficiency leads to induction of FGF21 mRNA expression in…”
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Endocrine Protection of Ischemic Myocardium by FGF21 from the Liver and Adipose Tissue
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“It was previously reported that cardiac expression of PGC1α is repressed by hypertrophic (18) and pro-inflammatory stimuli (19, 20).”
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Doroudgar, S., & Glembotski, C. C. (2011) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2010.12.003 · Cited by 117
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“Cardiomyokines have been estimated to number between 30 and 60, and include growth factors, endocrine hormones, and cytokines (58, 59).”
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“Moreover, plasma FGF21 levels have been linked to a higher risk of cardiovascular events in patients with type 2 diabetes (52).”
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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).”
BackgroundFGF 21 deletion exacerbates diabetic cardiomyopathy by aggravating cardiac lipid accumulation
Yan, X., Chen, J., Zhang, C., Zhou, S., Zhang, Z., Chen, J., Feng, W., Li, X., & Tan, Y. (2015) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.12530 · Cited by 85 · cited 1×
“Moreover, FGF21 deletion in mice exacerbates diabetic cardiomyopathy by aggravating cardiac lipid accumulation, although it is not clear whether this is a direct effect of the lack of FGF21 action on heart or indirect due to altered systemic lipid homeostasis in diabetic FGF21-null mice (31).”
BackgroundCardioprotective proteins upregulated in the liver in response to experimental myocardial ischemia
Liu, S. Q., Tefft, B. J., Roberts, D., Zhang, L., Ren, Y., Li, Y. C., Huang, Y., Zhang, D., Phillips, H. R., & Wu, Y. H. (2012) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00362.2012 · Cited by 78 · cited 1×
“One such protein identified by microarray-based gene expression profiling and protein analysis is FGF21 (33, 34), which was found to be highly increased at the protein level in the liver and also in adipose tissue after myocardial infarction.”
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“Interestingly, a recent study reported that serum FGF21 levels are independently associated with acute myocardial infarction (54), showing that serum FGF21 levels are markedly increased on the first day after the onset of myocardial infarction and remain high on days 3 and 7; moreover, FGF21 levels were found to be cl…”
BackgroundFibroblast growth factor 21 is induced upon cardiac stress and alters cardiac lipid homeostasis
Brahma, M. K., Adam, R. C., Pollak, N. M., Jaeger, D., Zierler, K. A., Poecher, N., Schreiber, R., Romauch, M., Moustafa, T., Eder, S., et al. (2014) · Journal of Lipid Research · doi:10.1194/jlr.m044784 · Cited by 70 · cited 3×
“Finally, it has been proposed that FGF21 is involved in modulating cardiac lipid metabolism and homeostasis (25).”
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“Cardiomyokines have been estimated to number between 30 and 60, and include growth factors, endocrine hormones, and cytokines (58, 59).”
BackgroundSerum fibroblast growth factor 21 levels are increased in atrial fibrillation patients
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“In addition, serum FGF21 levels are elevated in atrial fibrillation patients in association with atrial remodeling (53).”
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Fibroblast Growth Factor‐21 and the Beneficial Effects of Long‐Chain n‐3 Polyunsaturated Fatty Acids
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Self-citationHepatic FGF21 production is increased in late pregnancy in the mouse
Cui, Y., Giesy, S. L., Hassan, M., Davis, K., Zhao, S., & Boisclair, Y. R. (2014) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00554.2013 · Cited by 21
Liver cell-mediated alleviation of acute ischemic myocardial injury
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“One such protein identified by microarray-based gene expression profiling and protein analysis is FGF21 (33, 34), which was found to be highly increased at the protein level in the liver and also in adipose tissue after myocardial infarction.”
BackgroundShamagian, L. G., Romo, A. I., Castro, A. A. D. M., Alonso, J. A. B., Sáez, A. O., Blázquez, I. T. G., Sepulveda, J. A. S., Verdes, M. B. C., Correa, A. S., & Juan‐Salvadores, P. (2014) · European Heart Journal · doi:10.1093/eurheartj/ehu324 · Cited by 9
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“FGF15/19 typically activates FGFR4 with βKlotho as an endocrine signal (Itoh et al., 2015).”
BackgroundInfluential‘Browning’ the cardiac and peri-vascular adipose tissues to modulate cardiovascular risk
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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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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