Adapting to the cold: A role for endogenous fibroblast growth factor 21 in thermoregulation?
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Fibroblast growth factor 21 (FGF21) is in biomedical focus as a treatment option for metabolic diseases, given that administration improves metabolism in mice and humans. The metabolic effects of exogenous FGF21 administration are well-characterized, but the physiological role of endogenous FGF21 has not been fully understood yet. Despite cold-induced FGF21 expression and increased circulating levels in some studies, which co-occur with brown fat thermogenesis, recent studies in cold-acclimated mice demonstrate the dispensability of FGF21 for maintenance of body temperature, thereby questioning FGF21's role for thermogenesis. Here we discuss the evidence either supporting or opposing the role of endogenous FGF21 for thermogenesis based on the current literature. FGF21, secreted by brown fat or liver, is likely not required for energy homeostasis in the cold, but the nutritional conditions could modulate the interaction between FGF21, energy metabolism, and thermoregulation.
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FGF21 is an important therapeutic target of protection against muscle and liver insulin resistance induced by lipids and DM2.
“As such, it is an important therapeutic target of protection against muscle and liver insulin resistance induced by lipids and DM2 [106,107].”
From Adipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions (2021) · cites this paper as [107]
FGF21 is essential for controlling glucose and lipid metabolism.
“Substances that act as adipokines, myokines, and hepatokines, such as FGF21, are essential for controlling glucose and lipid metabolism.”
From Adipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions (2021) · cites this paper as [107]
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Fang, Y., Medina, D., Stockwell, R., McFadden, S., Hascup, E. R., Hascup, K. N., & Bartke, A. (2022) · GeroScience · doi:10.1007/s11357-022-00706-0 · Cited by 3 · see citing works
Frontiers in metabolic physiology grand challenges
Imig, J. D. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.879617 · Cited by 2 · see citing works
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Fibroblast growth factor 21: a novel link in the development and treatment of metabolic disorders
Mikhailova, A. A., Sharypova, M. V., Симаненкова, А. В., Cheburkin, Y. V., Станиславовна, Ф. О., Тимкина, Н. В., Dyachuk, V. A., & Каронова, Т. Л. (2025) · Arterial’naya Gipertenziya (Arterial Hypertension) · doi:10.18705/1607-419x-2024-2455 · Cited by 1 · see citing works
Effect of breeds on heat-evoked gene responses in sheep adipose tissue
ZHANG, D., PAN, I., Zhou, H., & Cao, Y. (2021) · TURKISH JOURNAL OF ZOOLOGY · doi:10.3906/zoo-2104-3
Stilgenbauer, L., de Lima, J. B. M., Debarba, L. K., Khan, M. M., Koshko, L., Kopchick, J. J., Bartke, A., Schneider, A., & Sadagurski, M. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.08.31.506031
Pregnancy negates thyroid hormone-induced pyrexia
López‐Alcántara, N., Adam, L., Resch, J., Keipert, S., Mittag, J., & Oelkrug, R. (2026) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00569.2025
Cycle-Synchronized Nutrition: Personalization of Dietary Strategies Based on Endocrine Dynamics
Chrystofiak, J. M., Golak, I., Włoszczak, W., Dydoń-Pikor, M., Zaworska, J. L., Kawecki, M., Biały, M., Warda, J., Zajączkowski, F., & Banasik, W. P. (2026) · Humanities & Social Sciences Reviews · doi:10.18510/hssr.2026.14213
Biological functions and emerging interplay of FGF21 and GDF15 in metabolic diseases and aging
Salmón‐Gómez, L., Keipert, S., Catalán, V., Rodrı́guez, A., Becerril, S., Frühbeck, G., & Gómez‐Ambrosi, J. (2026) · Molecular Biomedicine · doi:10.1186/s43556-026-00627-w
- Authors
- Klein Hazebroek, M., & Keipert, S.
- Affiliations
- Stockholm University (SE)
- Corresponding author
- Keipert, Susanne
- ORCID
- Keipert, Susanne
- Venue
- Frontiers in Endocrinology
- Publisher
- Frontiers Media SA
- Published
- 2020-07-02
- Volume
- 11
- Pages
- 389-389
- ISSN
- 1664-2392 (ISSN-L)
- PMC
- PMC7343899
- OpenAlex
- W3040335728
- Cited by
- 27
- References
- 58
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 5 · 2023: 2 · 2022: 6 · 2021: 8 · 2020: 1
- FWCI
- 0.41
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Endocrinology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Stockholms Universitet
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Thermal Regulation in Medicine
- Keywords
- FGF21, thermoregulation, thermogenesis, brown adipose tissue, cold acclimation, energy homeostasis, metabolic disorders, nutritional status, liver, energy metabolism
- MeSH terms
- Animals, Body Temperature Regulation, Adipose Tissue, Brown, Cold Temperature, Endocrine System, Energy Metabolism, Fibroblast Growth Factors, Humans, Liver, Paracrine Communication
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