Changes in liver metabolic pathways demonstrate efficacy of the combined dietary and microbial therapeutic intervention in MASLD mouse model.

Autor:	Iannone V; School of Medicine, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70200 Kuopio, Finland., Babu AF; School of Medicine, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70200 Kuopio, Finland; Afekta Technologies Ltd., Microkatu 1, 70210 Kuopio, Finland., Lok J; School of Medicine, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70200 Kuopio, Finland., Gómez-Gallego C; School of Medicine, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70200 Kuopio, Finland. Electronic address: carlos.gomezgallego@uef.fi., D'Auria G; Sequencing and Bioinformatics Service, Foundation for the Promotion of Health and Biomedical Research of Valencia Region, FISABIO, 46020 Valencia, Spain; CIBER in Epidemiology and Public Health (CIBERESP), Instituto de Salud Carlos III, 28029, Madrid, Spain., Vazquez-Uribe R; Technical University of Denmark, The Novo Nordisk Foundation Center for Biosustainability, 2800 Kongens Lyngby, Denmark., Vaaben TH; Technical University of Denmark, The Novo Nordisk Foundation Center for Biosustainability, 2800 Kongens Lyngby, Denmark., Bongers M; Technical University of Denmark, The Novo Nordisk Foundation Center for Biosustainability, 2800 Kongens Lyngby, Denmark., Mikkonen S; University Department of Technical Physics, University of Eastern Finland, 70211 Kuopio, Finland., Vaittinen M; School of Medicine, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70200 Kuopio, Finland., Tikkanen I; School of Medicine, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70200 Kuopio, Finland., Kettunen M; Biomedical Imaging Unit, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211, Kuopio, Finland., Klåvus A; Afekta Technologies Ltd., Microkatu 1, 70210 Kuopio, Finland., Sehgal R; School of Medicine, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70200 Kuopio, Finland., Kaminska D; School of Medicine, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70200 Kuopio, Finland; Department of Medicine, Division of Cardiology, University of California, Los Angeles, CA 90095, USA., Pihlajamaki J; School of Medicine, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70200 Kuopio, Finland; Department of Medicine, Endocrinology and Clinical Nutrition, Kuopio University Hospital, 70210 Kuopio, Finland., Hanhineva K; School of Medicine, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70200 Kuopio, Finland; Afekta Technologies Ltd., Microkatu 1, 70210 Kuopio, Finland; Department of Life Technologies, Food Sciences Unit, University of Turku, 20014 Turku, Finland., El-Nezami H; School of Medicine, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70200 Kuopio, Finland; University of Hong Kong, Hong Kong SAR, Molecular and Cell Biology Research Area, School of Biological Sciences, Hong Kong, Hong Kong, China., Sommer MOA; Technical University of Denmark, The Novo Nordisk Foundation Center for Biosustainability, 2800 Kongens Lyngby, Denmark. Electronic address: msom@bio.dtu.dk., Kolehmainen M; School of Medicine, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70200 Kuopio, Finland.
Jazyk:	angličtina
Zdroj:	Molecular metabolism [Mol Metab] 2023 Dec; Vol. 78, pp. 101823. Date of Electronic Publication: 2023 Oct 14.
DOI:	10.1016/j.molmet.2023.101823
Abstrakt:	Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is the most prevalent liver disease globally, yet no therapies are approved. The effects of Escherichia coli Nissle 1917 expressing aldafermin, an engineered analog of the intestinal hormone FGF19, in combination with dietary change were investigated as a potential treatment for MASLD. Methods: MASLD was induced in C57BL/6J male mice by American lifestyle-induced obesity syndrome diet and then switched to a standard chow diet for seven weeks. In addition to the dietary change, the intervention group received genetically engineered E. coli Nissle expressing aldafermin, while control groups received either E. coli Nissle vehicle or no treatment. MASLD-related plasma biomarkers were measured using an automated clinical chemistry analyzer. The liver steatosis was assessed by histology and bioimaging analysis using Fiji (ImageJ) software. The effects of the intervention in the liver were also evaluated by RNA sequencing and liquid-chromatography-based non-targeted metabolomics analysis. Pathway enrichment studies were conducted by integrating the differentially expressed genes from the transcriptomics findings with the metabolites from the metabolomics results using Ingenuity pathway analysis. Results: After the intervention, E. coli Nissle expressing aldafermin along with dietary changes reduced body weight, liver steatosis, plasma aspartate aminotransferase, and plasma cholesterol levels compared to the two control groups. The integration of transcriptomics with non-targeted metabolomics analysis revealed the downregulation of amino acid metabolism and related receptor signaling pathways potentially implicated in the reduction of hepatic steatosis and insulin resistance. Moreover, the downregulation of pathways linked to lipid metabolism and changes in amino acid-related pathways suggested an overall reduction of oxidative stress in the liver. Conclusions: These data support the potential for using engineered microbial therapeutics in combination with dietary changes for managing MASLD. Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.)
Databáze:	MEDLINE
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