Details zur Publikation |
Kategorie | Textpublikation |
Referenztyp | Zeitschriften |
DOI | 10.1016/j.ebiom.2024.105458 |
Lizenz ![]() |
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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 |