Details zur Publikation

Kategorie Textpublikation
Referenztyp Zeitschriften
DOI 10.1016/j.ebiom.2024.105458
Lizenz creative commons licence
Titel (primär) FGF21 and its underlying adipose tissue-liver axis inform cardiometabolic burden and improvement in obesity after metabolic surgery
Autor Patt, M.; Karkossa, I.; Krieg, L.; Massier, L.; Makki, K.; Tabei, S.; Karlas, T.; Dietrich, A.; Gericke, M.; Stumvoll, M.; Blüher, M.; von Bergen, M.; Schubert, K.; Kovacs, P.; Chakaroun, R.M.
Quelle EBioMedicine
Erscheinungsjahr 2024
Department iDiv; MOLTOX
Band/Volume 110
Seite von art. 105458
Sprache englisch
Topic T9 Healthy Planet
Supplements https://ars.els-cdn.com/content/image/1-s2.0-S2352396424004948-figs1_lrg.jpg
https://ars.els-cdn.com/content/image/1-s2.0-S2352396424004948-mmc1.docx
Keywords Metabolic surgery; Insulin resistance; Obesity; Metabolic disease; Adipose tissue; FGF21; Inter-organ crosstalk
Abstract Background
This research investigates the determinants of circulating FGF21 levels in a cohort reflecting metabolic disease progression, examining the associations of circulating FGF21 with morphology and function of adipose tissue (AT), and with metabolic adjustments following metabolic surgery.
Methods
We measured serum FGF21 in 678 individuals cross-sectionally and in 189 undergoing metabolic surgery longitudinally. Relationships between FGF21 levels, AT histology, transcriptomes and proteomes, cardiometabolic risk factors, and post-surgery metabolic adjustments were assessed using univariate and multivariate analyses, causal mediation analysis, and network integration of AT transcriptomes and proteomes.
Findings
FGF21 levels were linked to central adiposity, subclinical inflammation, insulin resistance, and cardiometabolic risk, and were driven by circulating leptin and liver enzymes. Higher FGF21 were linked with AT dysfunction reflected in fibro-inflammatory and lipid dysmetabolism pathways. Specifically, visceral AT inflammation was tied to both FGF21 elevation and liver dysfunction. Post-surgery, FGF21 peaked transitorily at three months. Mediation analysis highlighted an underlying increased AT catabolic state with elevated free fatty acids (FFA), contributing to higher liver stress and FGF21 levels (total effect of free fatty acids on FGF21 levels: 0.38, p < 0.01; proportion mediation via liver 32%, p < 0.01). In line with this, histological AT fibrosis linked with less pronounced FGF21 responses and reduced fat loss post-surgery (FFA and visceral AT fibrosis: rho = −0.31, p = 0.030; FFA and fat-mass loss: rho = 0.17, p = 0.020).
Interpretation
FGF21 reflects the liver's disproportionate metabolic stress response in both central adiposity and after metabolic surgery, with its dynamics reflecting an AT-liver crosstalk.
dauerhafte UFZ-Verlinkung https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=29249
Patt, M., Karkossa, I., Krieg, L., Massier, L., Makki, K., Tabei, S., Karlas, T., Dietrich, A., Gericke, M., Stumvoll, M., Blüher, M., von Bergen, M., Schubert, K., Kovacs, P., Chakaroun, R.M. (2024):
FGF21 and its underlying adipose tissue-liver axis inform cardiometabolic burden and improvement in obesity after metabolic surgery
EBioMedicine 110 , art. 105458 10.1016/j.ebiom.2024.105458