Endocrine fibroblast growth factors 15/19 and 21: from feast to famine
Open accessAbstract
We review the physiology and pharmacology of two atypical fibroblast growth factors (FGFs)—FGF15/19 and FGF21—that can function as hormones. Both FGF15/19 and FGF21 act on multiple tissues to coordinate carbohydrate and lipid metabolism in response to nutritional status. Whereas FGF15/19 is secreted from the small intestine in response to feeding and has insulin-like actions, FGF21 is secreted from the liver in response to extended fasting and has glucagon-like effects. FGF21 also acts in an autocrine fashion in several tissues, including adipose. The pharmacological actions of FGF15/19 and FGF21 make them attractive drug candidates for treating metabolic disease.
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Bile acids are endogenous ligands of FXR, and their activation results in release of FGF19.
“They are endogenous ligands of the farnesoid X receptor (FXR), their activation of FXR resulting in the release of fibroblast growth factor (FGF) 1943.”
From Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future (2014) · cites this paper as [43]
The FGF19 subfamily of FGFs has reduced affinity for HSGAGs and diffuses into circulation to act on distal tissues, thus functioning as endocrine hormones.
“Unlike traditional FGFs, however, the FGF19 subfamily of FGFs, consisting of FGF19, FGF21, and FGF23, has reduced affinity for HSGAGs and diffuses into circulation to act on distal tissues (9, 106). Thus, these FGFs function as endocrine hormones.”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [106]
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- Authors
- Potthoff, M. J., Kliewer, S. A., & Mangelsdorf, D. J.
- Affiliations
- Howard Hughes Medical Institute (US)
- The University of Texas Southwestern Medical Center (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2012-02-02
- Volume
- 26
- Issue
- 4
- Pages
- 312-324
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC3289879
- OpenAlex
- W2099579483
- Cited by
- 442
- References
- 141
- Citations by year
- 2026: 19 · 2025: 13 · 2024: 30 · 2023: 16 · 2022: 37 · 2021: 30 · 2020: 29 · 2019: 27 · 2018: 39 · 2017: 41 · 2016: 28 · 2015: 36 · 2014: 46 · 2013: 37 · 2012: 12
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute (I-1558, I-1275)
- Welch Foundation (I-1275, I-1558)
- National Institutes of Health (I-1275, I-1558)
- National Institute of General Medical Sciences (RL1GM084436)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK067158)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Rheumatology › GDF15 and Related Biomarkers
- Health Sciences › Medicine › Nephrology › Parathyroid Disorders and Treatments
- Keywords
- FGF15/19, FGF21, carbohydrate metabolism, lipid metabolism, nutritional status, fasting, insulin-like activity, autocrine signaling, adipose tissue, small intestine, liver
- MeSH terms
- Animals, Bile Acids and Salts, Fasting, Fibroblast Growth Factors, Homeostasis, Humans, Neoplasms
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