{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T07:14:31Z","timestamp":1792134871006,"version":"4.4.0"},"reference-count":29,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T00:00:00Z","timestamp":1693958400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ANR-Hepatobrain"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common cause of chronic liver disease worldwide, affecting 70\u201390% of obese individuals. In humans, a lower NAFLD incidence is reported in pre-menopausal women, although the mechanisms affording this protection remain under-investigated. Here, we tested the hypothesis that the constitutive androstane nuclear receptor (CAR) plays a role in the pathogenesis of experimental NAFLD. Male and female wild-type (WT) and CAR knock-out (CAR\u2212\/\u2212) mice were subjected to a high-fat diet (HFD) for 16 weeks. We examined the metabolic phenotype of mice through body weight follow-up, glucose tolerance tests, analysis of plasmatic metabolic markers, hepatic lipid accumulation, and hepatic transcriptome. Finally, we examined the potential impact of HFD and CAR deletion on specific brain regions, focusing on glial cells. HFD-induced weight gain and hepatic steatosis are more pronounced in WT males than females. CAR\u2212\/\u2212 females present a NASH-like hepatic transcriptomic signature suggesting a potential NAFLD to NASH transition. Transcriptomic correlation analysis highlighted a possible cross-talk between CAR and ER\u03b1 receptors. The peripheral effects of CAR deletion in female mice were associated with astrogliosis in the hypothalamus. These findings prove that nuclear receptor CAR may be a potential mechanism entry-point and a therapeutic target for treating NAFLD\/NASH.<\/jats:p>","DOI":"10.3390\/cells12182218","type":"journal-article","created":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T10:14:14Z","timestamp":1693995254000},"page":"2218","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["CAR Protects Females from Diet-Induced Steatosis and Associated Metabolic Disorders"],"prefix":"10.3390","volume":"12","author":[{"given":"Fabiana","family":"Oliviero","sequence":"first","affiliation":[{"name":"Toxalim (Research Centre in Food Toxicology), Universit\u00e9 de Toulouse, INRAE, ENVT, INP-Purpan, UPS, 31027 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy","family":"Klement","sequence":"additional","affiliation":[{"name":"Institute of Functional Genomics, University of Montpellier, CNRS, INSERM, 34094 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucile","family":"Mary","sequence":"additional","affiliation":[{"name":"Toxalim (Research Centre in Food Toxicology), Universit\u00e9 de Toulouse, INRAE, ENVT, INP-Purpan, UPS, 31027 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yannick","family":"Dauwe","sequence":"additional","affiliation":[{"name":"Toxalim (Research Centre in Food Toxicology), Universit\u00e9 de Toulouse, INRAE, ENVT, INP-Purpan, UPS, 31027 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yannick","family":"Lippi","sequence":"additional","affiliation":[{"name":"Toxalim (Research Centre in Food Toxicology), Universit\u00e9 de Toulouse, INRAE, ENVT, INP-Purpan, UPS, 31027 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Naylies","sequence":"additional","affiliation":[{"name":"Toxalim (Research Centre in Food Toxicology), Universit\u00e9 de Toulouse, INRAE, ENVT, INP-Purpan, UPS, 31027 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Gayrard","sequence":"additional","affiliation":[{"name":"Toxalim (Research Centre in Food Toxicology), Universit\u00e9 de Toulouse, INRAE, ENVT, INP-Purpan, UPS, 31027 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Marchi","sequence":"additional","affiliation":[{"name":"Toxalim (Research Centre in Food Toxicology), Universit\u00e9 de Toulouse, INRAE, ENVT, INP-Purpan, UPS, 31027 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laila","family":"Mselli-Lakhal","sequence":"additional","affiliation":[{"name":"Toxalim (Research Centre in Food Toxicology), Universit\u00e9 de Toulouse, INRAE, ENVT, INP-Purpan, UPS, 31027 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1002\/hep.26156","article-title":"Association Between Noninvasive Fibrosis Markers and Mortality Among Adults With Nonalcoholic Fatty Liver Disease in the United States","volume":"57","author":"Kim","year":"2013","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1007\/s12325-017-0556-1","article-title":"NAFLD as a Sexual Dimorphic Disease: Role of Gender and Reproductive Status in the Development and Progression of Nonalcoholic Fatty Liver Disease and Inherent Cardiovascular Risk","volume":"34","author":"Ballestri","year":"2017","journal-title":"Adv. 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