| Title: |
Circulating FGF21 and Ketone Bodies Modify the Risk of MASLD and Mortality:Insights from the PREVEND Cohort Study |
| Authors: |
Chvatal-Medina, Mateo; Li, Yakun; Dam, Wendy A; Connelly, Margery A; Moshage, Han; Bakker, Stephan J L; Dullaart, Robin P F; Post, Adrian |
| Source: |
Chvatal-Medina, M, Li, Y, Dam, W A, Connelly, M A, Moshage, H, Bakker, S J L, Dullaart, R P F & Post, A 2025, 'Circulating FGF21 and Ketone Bodies Modify the Risk of MASLD and Mortality : Insights from the PREVEND Cohort Study', International Journal of Molecular Sciences, vol. 26, no. 11, 5059. https://doi.org/10.3390/ijms26115059 |
| Publication Year: |
2025 |
| Collection: |
University of Groningen research database |
| Subject Terms: |
Humans; Fibroblast Growth Factors/blood; Ketone Bodies/blood; Male; Female; Middle Aged; Biomarkers/blood; Cohort Studies; Aged; Fatty Liver/blood; Risk Factors |
| Description: |
Fibroblast growth factor 21 (FGF21) and ketone bodies are markers of metabolic dysregulation, independently associated with metabolic-dysfunction-associated steatotic liver disease (MASLD) and mortality. We studied their interaction with MASLD and all-cause mortality in 6025 participants from the Prevention of Renal and Vascular End-stage Disease (PREVEND) cohort. Plasma FGF21 (immunoassay) and ketone body concentrations (nuclear magnetic resonance spectroscopy) were measured at baseline. A Fatty Liver Index ≥60 was used as a proxy of MASLD. Logistic regression assessed associations with MASLD, and Cox models evaluated all-cause mortality over a median follow-up of 10.3 years. FGF21 and ketone bodies were not correlated (r = 0.02, p = 0.06), but FGF21 (OR: 1.93 [1.81-2.05], p < 0.001) and ketone bodies (OR: 1.29 [1.19-2.05], p < 0.001) were independent of each other associated with MASLD, with a positive interaction ( p = 0.004). Higher FGF21 (HR: 1.24, 95% CI: 1.16-1.32, p < 0.001) and ketone bodies (HR: 1.46, 95% CI: 1.34-1.59, p < 0.001) were associated with mortality, as well as with a positive interaction ( p = 0.038). After adjustment for potential confounders, only ketone bodies remained independently associated, while the association of FGF21 became dependent on ketone body levels (interaction p = 0.005). These biomarkers may serve as integrated metabolic stress markers, improving risk stratification for MASLD and adverse outcomes. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
1422-0067 |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/40507869; info:eu-repo/semantics/altIdentifier/hdl/https://hdl.handle.net/11370/4e12e9b6-86fb-44ca-8f67-cab6b8ec3bd3; info:eu-repo/semantics/altIdentifier/pissn/1422-0067 |
| DOI: |
10.3390/ijms26115059 |
| Availability: |
https://hdl.handle.net/11370/4e12e9b6-86fb-44ca-8f67-cab6b8ec3bd3; https://research.rug.nl/en/publications/4e12e9b6-86fb-44ca-8f67-cab6b8ec3bd3; https://doi.org/10.3390/ijms26115059; https://pure.rug.nl/ws/files/1330118440/ijms-26-05059.pdf |
| Rights: |
info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.D8386D63 |
| Database: |
BASE |