Haag, Mathias and Winter, Stefan and Kemas, Aurino M. and Tevini, Julia and Feldman, Alexandra and Eder, Sebastian K. and Felder, Thomas K. and Datz, Christian and Paulweber, Bernhard and Liebisch, Gerhard and Burk, Oliver and Lauschke, Volker M. and Aigner, Elmar and Schwab, Matthias (2025) Circulating metabolite signatures indicate differential gut-liver crosstalk in lean and obese MASLD. JCI INSIGHT, 10 (8): e180943. ISSN , 2379-3708
Full text not available from this repository. (Request a copy)Abstract
BACKGROUND. Alterations in circulating metabolites have been described in obese metabolic dysfunction-associated steatotic liver disease (MASLD), but data on lean MASLD are lacking. We investigated serum metabolites, including microbial bile acids and short-chain fatty acids (SCFAs), and their association with lean and obese MASLD. METHODS. Serum samples from 204 people of European descent were allocated to four groups: lean healthy, lean MASLD, obese healthy, and obese MASLD. Liquid chromatography-mass spectrometry-based metabolomics and linear model analysis were performed. MASLD prediction was assessed based on least absolute shrinkage and selection operator regression. Functional effects of altered molecules were verified in organotypic 3D primary human liver cultures. RESULTS. Lean MASLD was characterized by elevated isobutyrate, methionine sulfoxide, propionate, and phosphatidylcholines. Patients with obese MASLD had increased sarcosine and decreased lysine and asymmetric dimethylarginine. Using metabolites, sex, and BMI, MASLD versus healthy could be predicted with a median AUC of 86.5% and 85.6% in the lean and obese subgroups, respectively. Functional experiments in organotypic 3D primary human liver cultures showed propionate and isobutyrate induced lipid accumulation and altered expression of genes involved in lipid and glucose metabolism. CONCLUSION. Lean MASLD is characterized by a distinct metabolite pattern related to amino acid metabolism, lipids, and SCFAs, while metabolic pathways of lipid accumulation are differentially activated by microbial metabolites. We highlight an important role of microbial metabolites in MASLD, with implications for predictive and mechanistic assessment of liver disease across weight categories. FUNDING. Robert Bosch Stiftung, Swedish Research Council (2021-02801, 2023-03015, 2024-03401), ERC Consolidator Grant 3DMASH (101170408), Ruth and Richard Julin Foundation for Gastroenterology (2021-00158), SciLifeLab and Wallenberg National Program for Data-Driven Life Science (WASPDDLS22:006), Novo Nordisk Foundation (NNF23OC0085944, NNF23OC0084420), PMU-FFF (E-18/28/148-FEL).
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CHAIN FATTY-ACIDS; N-METHYLTRANSFERASE; BILE-ACIDS; DISEASE; GENDER; TRANSPORTERS; MICROBIOME; MECHANISMS; RECEPTORS; SUBTYPES; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Apr 2026 11:45 |
| Last Modified: | 20 Apr 2026 11:45 |
| URI: | https://pred.uni-regensburg.de/id/eprint/67616 |
Actions (login required)
 |
View Item |
