ArticleThe Biochemical journal2016
Circulating FGF21 proteolytic processing mediated by fibroblast activation protein.
Article in The Biochemical journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
72 citing papers in PubMed, 122 citations in OpenAlex.
- Effect of exercise on Fibroblast Growth Factor 21 levels in healthy males and females.PloS one · 2025Trial
- Meal sugar-protein balance determines postprandial FGF21 response in humans.American journal of physiology. Endocrinology and metabolism · 2023Trial
- FGF21 contributes to metabolic improvements elicited by combination therapy with exenatide and pioglitazone in patients with type 2 diabetes.American journal of physiology. Endocrinology and metabolism · 2022Trial
- Effects of interleukin-1 antagonism and corticosteroids on fibroblast growth factor-21 in patients with metabolic syndrome.Scientific reports · 2021Trial
- Trial
- Antibody-mediated activation of the FGFR1/Klothoβ complex corrects metabolic dysfunction and alters food preference in obese humans.Proceedings of the National Academy of Sciences of the United States of America · 2020Trial
- Review
- Beneficial Hepatokines in MASLD/MASH: Therapeutic Potentials and Drug Delivery Challenges.International journal of molecular sciences · 2026Review
- Influence of Fibroblast Growth Factor 21 on Delayed Glycemic Improvement Following Acute Exercise in Type 2 Diabetes Mellitus.Diabetes & metabolism journal · 2026Article
- Screening and validation of rabbit monoclonal antibody pair against human FGF21 for human plasma FGF21 high sensitivity bioanalysis.iScience · 2026Article
- Serum fibroblast growth factor 21 is a novel biomarker of cachexia in chronic liver disease.Frontiers in nutrition · 2026Article
- Antifibrotic therapies for metabolic dysfunction-associated steatotic liver disease.JHEP reports : innovation in hepatology · 2025Review
- Treating metabolic dysfunction-associated steatohepatitis: The fat-trimming FGF21 approach.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025Review
- Bioinformatics-based screening and validation of ferroptosis-related genes in sepsis and type 2 diabetes mellitus.Experimental biology and medicine (Maywood, N.J.) · 2025Article
- Research progress on the role of FGF21 in insulin resistance.Frontiers in endocrinology · 2025Review
- Distinct genetic signals at the FGF21 locus complicate studies of FGF21's role in diet regulation using human cohort data.Molecular metabolism · 2024Article
- Development of Zalfermin, a Long-Acting Proteolytically Stabilized FGF21 Analog.Journal of medicinal chemistry · 2024Article
- From basic research to clinical application: targeting fibroblast activation protein for cancer diagnosis and treatment.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- The cross talk between type II diabetic microenvironment and the regenerative capacities of human adipose tissue-derived pericytes: a promising cell therapy.Stem cell research & therapy · 2024Article
- Seladelpar combined with complementary therapies improves fibrosis, inflammation, and liver injury in a mouse model of nonalcoholic steatohepatitis.American journal of physiology. Gastrointestinal and liver physiology · 2024Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fibroblast growth factor 21 (FGF21), a hormone implicated in the regulation of glucose homoeostasis, insulin sensitivity, lipid metabolism and body weight, is considered to be a promising therapeutic target for the treatment of metabolic disorders. Despite observations that FGF21 is rapidly proteolysed in circulation rending it potentially inactive, little is known regarding mechanisms by which FGF21 protein levels are regulated. We systematically investigated human FGF21 protein processing using mass spectrometry. In agreement with previous reports, circulating human FGF21 was found to be cleaved primarily after three proline residues at positions 2, 4 and 171. The extent of FGF21 processing was quantified in a small cohort of healthy human volunteers. Relative abundance of FGF21 proteins cleaved after Pro-2, Pro-4 and Pro-171 ranged from 16 to 30%, 10 to 25% and 10 to 34%, respectively. Dipeptidyl peptidase IV (DPP-IV) was found to be the primary protease responsible for N-terminal cleavages after residues Pro-2 and Pro-4. Importantly, fibroblast activation protein (FAP) was implicated as the protease responsible for C-terminal cleavage after Pro-171, rendering the protein inactive. The requirement of FAP for FGF21 proteolysis at the C-terminus was independently demonstrated by in vitro digestion, immunodepletion of FAP in human plasma, administration of an FAP-specific inhibitor and by human FGF21 protein processing patterns in FAP knockout mouse plasma. The discovery that FAP is responsible for FGF21 inactivation extends the FGF21 signalling pathway and may enable novel approaches to augment FGF21 actions for therapeutic applications.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.