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Foundation","award":["10.13039\/501100011033"],"award-info":[{"award-number":["10.13039\/501100011033"]}],"id":[{"id":"https:\/\/ror.org\/018d7k032","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Conchita R\u00e1bago Foundation","award":["1381179-R"],"award-info":[{"award-number":["1381179-R"]}],"id":[{"id":"https:\/\/ror.org\/018d7k032","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Conchita R\u00e1bago Foundation","award":["PIGE-0052-2020"],"award-info":[{"award-number":["PIGE-0052-2020"]}],"id":[{"id":"https:\/\/ror.org\/018d7k032","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms25052961","type":"journal-article","created":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T05:31:12Z","timestamp":1709530272000},"page":"2961","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Semaglutide Improves Liver Steatosis and De Novo Lipogenesis Markers in Obese and Type-2-Diabetic Mice with Metabolic-Dysfunction-Associated Steatotic Liver Disease"],"prefix":"10.3390","volume":"25","author":[{"given":"Manuel","family":"Soto-Catal\u00e1n","sequence":"first","affiliation":[{"name":"Renal, Vascular and Diabetes Research Laboratory, IIS-Fundaci\u00f3n Jim\u00e9nez D\u00edaz, Spanish Biomedical Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"},{"name":"Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3586-3319","authenticated-orcid":false,"given":"Lucas","family":"Opazo-R\u00edos","sequence":"additional","affiliation":[{"name":"Renal, Vascular and Diabetes Research Laboratory, IIS-Fundaci\u00f3n Jim\u00e9nez D\u00edaz, Spanish Biomedical Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"},{"name":"Facultad de Ciencias de la Salud, Universidad de Las Am\u00e9ricas, Concepci\u00f3n-Talcahuano 4301099, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hern\u00e1n","family":"Quiceno","sequence":"additional","affiliation":[{"name":"Department of Pathology, Fundaci\u00f3n Jim\u00e9nez D\u00edaz, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iolanda","family":"L\u00e1zaro","sequence":"additional","affiliation":[{"name":"Cardiovascular Risk and Nutrition Research Group, Epidemiology and Public Health Program, Hospital del Mar Medical Research Institute (IMIM), 08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7468-2871","authenticated-orcid":false,"given":"Juan Antonio","family":"Moreno","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Physiology and Immunology, University of Cordoba, 140471 Cordoba, Spain"},{"name":"Maim\u00f3nides Biomedical Research Institute of Cordoba (IMIBIC), Hospital Universitario Reina Sof\u00eda, 14004 C\u00f3rdoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9001-5414","authenticated-orcid":false,"given":"Carmen","family":"G\u00f3mez-Guerrero","sequence":"additional","affiliation":[{"name":"Renal, Vascular and Diabetes Research Laboratory, IIS-Fundaci\u00f3n Jim\u00e9nez D\u00edaz, Spanish Biomedical Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"},{"name":"Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"Egido","sequence":"additional","affiliation":[{"name":"Renal, Vascular and Diabetes Research Laboratory, IIS-Fundaci\u00f3n Jim\u00e9nez D\u00edaz, Spanish Biomedical Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"},{"name":"Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6604-3327","authenticated-orcid":false,"given":"Sebastian","family":"Mas-Fontao","sequence":"additional","affiliation":[{"name":"Renal, Vascular and Diabetes Research Laboratory, IIS-Fundaci\u00f3n Jim\u00e9nez D\u00edaz, Spanish Biomedical Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"},{"name":"Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), 28029 Madrid, Spain"},{"name":"Faculty of Medicine and Biomedicine, Universidad Alfonso X el Sabio (UAX), 28691 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/S2468-1253(22)00165-0","article-title":"The prevalence and incidence of NAFLD worldwide: A systematic review and meta-analysis","volume":"7","author":"Riazi","year":"2022","journal-title":"Lancet Gastroenterol. 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