{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:43:58Z","timestamp":1791920638545,"version":"4.3.4"},"reference-count":38,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,5,24]],"date-time":"2023-05-24T00:00:00Z","timestamp":1684886400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>Various intracellular pathways regulate inflammation in NASH. Cyclic GMP\u2010AMP synthase (cGAS) is a DNA sensor that activates STING and plays a role in inflammatory diseases. Here, we explored the role of cGAS in hepatic damage, steatosis, inflammation, and liver fibrosis in mouse models of NASH.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>cGAS deficient (cGAS\u2010KO) and STING deficient (STING\u2010KO) mice received high fat\u2010high cholesterol\u2010high sugar diet (HF\u2010HC\u2010HSD) or relevant control diets. Livers were evaluated after 16 or 30\u2009weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>HF\u2010HC\u2010HSD diet, both at 16 and 30\u2009weeks, resulted in increased cGAS protein expression as well as in increased ALT, IL\u20101\u03b2, TNF\u2010\u03b1 and MCP\u20101 in wild\u2010type (WT) mice compared to controls. Surprisingly, liver injury, triglyceride accumulation, and inflammasome activation were greater in HF\u2010HC\u2010HSD cGAS\u2010KO compared to WT mice at 16 and to a lesser extent at 30\u2009weeks. STING, a downstream target of cGAS was significantly increased in WT mice after HF\u2010HC\u2010HSD. In STING\u2010KO mice after HF\u2010HC\u2010HSD feeding, we found increased ALT and attenuated MCP1 and IL\u20101\u03b2 expression compared to WT mice. Markers of liver fibrosis were increased in cGAS\u2010 and STING\u2010KO mice compared to WT on HF\u2010HC\u2010HSD. We discovered that cGAS\u2010KO mice had a significant increase in circulating endotoxin levels on HF\u2010HC\u2010HSD that correlated with changes in intestinal morphology which was exacerbated by HF\u2010HC\u2010HSD compared to WT mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings indicate that cGAS or STING deficiency exacerbate liver damage, steatosis, and inflammation in HF\u2010HC\u2010HSD diet\u2010induced NASH, which might be linked to the disruption of the gut barrier.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.15610","type":"journal-article","created":{"date-parts":[[2023,5,24]],"date-time":"2023-05-24T10:40:38Z","timestamp":1684924838000},"page":"1937-1949","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Protective role of <scp>cGAS<\/scp> in <scp>NASH<\/scp> is related to the maintenance of intestinal homeostasis"],"prefix":"10.1111","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9008-0128","authenticated-orcid":false,"given":"Marcelle","family":"de Carvalho\u00a0Ribeiro","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Gastroenterology and Hepatology Beth Israel Deaconess Medical Center and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeonhee","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Gastroenterology and Hepatology Beth Israel Deaconess Medical Center and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeeval","family":"Mehta","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Gastroenterology and Hepatology Beth Israel Deaconess Medical Center and Harvard Medical School  Boston Massachusetts 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