FGF21 and its underlying adipose tissue-liver axis inform cardiometabolic burden and improvement in obesity after metabolic surgery

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. We measured s...

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Bibliographic Details
Published in:EBioMedicine 2024-12, Vol.110, p.105458, Article 105458
Main Authors: Patt, Marie, Karkossa, Isabel, Krieg, Laura, Massier, Lucas, Makki, Kassem, Tabei, Shirin, Karlas, Thomas, Dietrich, Arne, Gericke, Martin, Stumvoll, Michael, Blüher, Matthias, von Bergen, Martin, Schubert, Kristin, Kovacs, Peter, Chakaroun, Rima M.
Format: Article
Language:English
Subjects:
Adipose tissue
Adipose Tissue - metabolism
Adult
Allmänmedicin
Biomarkers
Cardiometabolic Risk Factors
Cross-Sectional Studies
Female
FGF21
Fibroblast Growth Factors - blood
Fibroblast Growth Factors - metabolism
General Medicine
Humans
Insulin resistance
Inter-organ crosstalk
Liver - metabolism
Liver - pathology
Liver - surgery
Male
Metabolic disease
Metabolic surgery
Middle Aged
Obesity
Obesity - metabolism
Obesity - surgery
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Summary: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. 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. 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 
ISSN:2352-3964
2352-3964
DOI:10.1016/j.ebiom.2024.105458