Semaglutide improves liver steatosis and de novo lipogenesis markers in obese and type-2-diabetic mice with metabolic-dysfunction-associated steatotic liver disease

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• dc.contributor.author Soto-Catalán, Manuel
• dc.contributor.author Opazo Ríos, Lucas
• dc.contributor.author Quiceno, Hernán
• dc.contributor.author Lázaro, Iolanda
• dc.contributor.author Moreno, Juan Antonio
• dc.contributor.author Gómez Guerrero, Carmen
• dc.contributor.author Egido, Jesús (Egido de los Ríos)
• dc.contributor.author Mas Fontao, Sebastián
• dc.date.accessioned 2025-06-04T06:18:56Z
• dc.date.available 2025-06-04T06:18:56Z
• dc.date.issued 2024
• dc.description.abstract Metabolic-dysfunction-associated steatotic liver disease (MASLD) is a prevalent clinical condition associated with elevated morbidity and mortality rates. Patients with MASLD treated with semaglutide, a glucagon-like peptide-1 receptor agonist, demonstrate improvement in terms of liver damage. However, the mechanisms underlaying this beneficial effect are not yet fully elucidated. We investigated the efficacy of semaglutide in halting MASLD progression using a genetic mouse model of diabesity. Leptin-receptor-deficient mice with obesity and diabetes (BKS db/db) were either untreated or administered with semaglutide for 11 weeks. Changes in food and water intake, body weight and glycemia were monitored throughout the study. Body fat composition was assessed by dual-energy X-ray absorptiometry. Upon sacrifice, serum biochemical parameters, liver morphology, lipidomic profile and liver-lipid-related pathways were evaluated. The semaglutide-treated mice exhibited lower levels of glycemia, body weight, serum markers of liver dysfunction and total and percentage of fat mass compared to untreated db/db mice without a significant reduction in food intake. Histologically, semaglutide reduced hepatic steatosis, hepatocellular ballooning and intrahepatic triglycerides. Furthermore, the treatment ameliorated the hepatic expression of de novo lipogenesis markers and modified lipid composition by increasing the amount of polyunsaturated fatty acids. The administration of semaglutide to leptin-receptor-deficient, hyperphagic and diabetic mice resulted in the amelioration of MASLD, likely independently of daily caloric intake, suggesting a direct effect of semaglutide on the liver through modulation of the lipid profile.
• dc.description.sponsorship This research was funded by Instituto de Salud Carlos III (PI20/00375, PI20/00487, PI23/00119, PI23/00669), the Spanish Ministry of Science and Innovation/State Investigation Agency (10.13039/501100011033): MICINN-FEDER grants RTI2018-098788-B-I00, PID2021-127741OB-I00 and DTS19/00093, as well as supported the salary of JAM (RYC-2017-22369) (co-funded by the European Regional Development Fund/European Social Fund “A way to make Europe”/”Investing in your future”) Programa Operativo FEDER Junta de Andalucía (1381179-R) and Consejería de Salud y Familias-FEDER, Junta de Andalucía (PIGE-0052-2020), Spanish Biomedical Research Centre in diabetes and metabolic diseases (CIBERDEM), Spanish Society of Nephrology (SEN) and thank Conchita Rábago Foundation for M.S-C grant support.
• dc.format.mimetype application/pdf
• dc.identifier.citation Soto-Catalán M, Opazo-Ríos L, Quiceno H, Lázaro I, Moreno JA, Gómez-Guerrero C, et al. Semaglutide improves liver steatosis and de novo lipogenesis markers in obese and type-2-diabetic mice with metabolic-dysfunction-associated steatotic liver disease. Int J Mol Sci. 2024 Mar 4;25(5):2961. DOI: 10.3390/ijms25052961
• dc.identifier.doi http://dx.doi.org/10.3390/ijms25052961
• dc.identifier.issn 1422-0067
• dc.identifier.uri http://hdl.handle.net/10230/70604
• dc.language.iso eng
• dc.publisher MDPI
• dc.relation.ispartof Int J Mol Sci. 2024 Mar 4;25(5):2961
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/RTI2018-098788-B-I00
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2021-127741OB-I00
• dc.rights © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword GLP1 receptor agonists
• dc.subject.keyword Diabetes
• dc.subject.keyword Insulin resistance
• dc.subject.keyword Obesity
• dc.subject.keyword Semaglutide
• dc.subject.keyword Steatosis
• dc.title Semaglutide improves liver steatosis and de novo lipogenesis markers in obese and type-2-diabetic mice with metabolic-dysfunction-associated steatotic liver disease
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion