{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T17:30:39Z","timestamp":1772991039432,"version":"3.50.1"},"reference-count":57,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T00:00:00Z","timestamp":1741824000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T00:00:00Z","timestamp":1741824000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Notch1 protein plays a significant role in hepatic metabolism, as evidenced by its correlation with insulin resistance in the livers of obese individuals, making it an intriguing research target. Therefore, this study aims to investigate the impact of aerobic exercise on Notch1 pathways in the hepatic tissue of obese mice and its role in controlling hepatic metabolism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Therefore, we conducted a cross\u2010sectional study utilising liver biopsies from lean and obese humans, as well as an intervention study involving mice subjected to a high\u2010fat diet. The obese\u2010trained mice group underwent a treadmill\u2010running protocol for 4\u2009weeks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our findings revealed that obese individuals exhibited increased NOTCH1 mRNA levels compared to lean subjects. The detrimental effects of Notch1 signalling were confirmed by Notch1\u2010overexpressed HepG2 cell lines. Obese mice with higher hepatic Notch1 signalling demonstrated a reduction in this pathway when subjected to a 4\u2010week treadmill running. Another benefit noticed in this trained group was the amelioration of insulin resistance, as well as a reduction in pyruvate intolerance and gluconeogenic enzymes. Additionally, we observed that these protective findings were accompanied by a decrease in mTORC1 pathway activity and lipid accumulation in the liver. Pharmacological inhibition of Notch1 in obese mice led to an increase in mitochondrial respiration in the liver.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We conclude that Notch1 signalling may be a potentially useful therapeutic target in obesity, while aerobic exercise training suppresses the Notch1 pathway in the liver, contributing to the regulation of hepatic glucose and lipid metabolism in obese mice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70068","type":"journal-article","created":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T03:37:32Z","timestamp":1741837052000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Notch1 Signalling Is Downregulated by Aerobic Exercise, Leading to Improvement of Hepatic Metabolism in Obese Mice"],"prefix":"10.1111","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2208-3527","authenticated-orcid":false,"given":"Rafael Calais","family":"Gaspar","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Biology of Exercise University of Campinas (UNICAMP)  Limeira Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Paula Azev\u00eado","family":"Mac\u00eado","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology of Exercise University of Campinas (UNICAMP)  Limeira Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susana Castelo Branco Ramos","family":"Nakandakari","sequence":"additional","affiliation":[{"name":"Laboratory of Nutritional Genomics University of Campinas (UNICAMP)  Limeira Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4280-6558","authenticated-orcid":false,"given":"Vitor Rosetto","family":"Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology of Exercise University of Campinas (UNICAMP)  Limeira Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela Ferreira","family":"Abud","sequence":"additional","affiliation":[{"name":"School of Physical Education and Sport of Ribeirao Preto (EEFERP\/USP) University of Sao Paulo  Ribeirao Preto Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renan Fudoli Lins","family":"Vieira","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology of Exercise University of Campinas (UNICAMP)  Limeira Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivo Vieira","family":"de Sousa Neto","sequence":"additional","affiliation":[{"name":"School of Physical Education and Sport of Ribeirao Preto (EEFERP\/USP) University of Sao Paulo  Ribeirao Preto Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isadora Carolina Betim","family":"Pavan","sequence":"additional","affiliation":[{"name":"Multidisciplinary Laboratory of Food and Health (LABMAS), School of Applied Sciences (FCA) University of Campinas (UNICAMP)  Limeira Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luiz Guilherme Salvino","family":"da Silva","sequence":"additional","affiliation":[{"name":"Multidisciplinary Laboratory of Food and Health (LABMAS), School of Applied Sciences (FCA) University of Campinas (UNICAMP)  Limeira Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando Moreira","family":"Simabuco","sequence":"additional","affiliation":[{"name":"Multidisciplinary Laboratory of Food and Health (LABMAS), School of Applied Sciences (FCA) University of Campinas (UNICAMP)  Limeira Sao Paulo Brazil"},{"name":"Applied Molecular Signaling Laboratory (LabSIMA), Department of Biochemistry Federal University of S\u00e3o Paulo  Campinas Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9679-8357","authenticated-orcid":false,"given":"Adelino S. 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