Pathology of the liver in obese and diabetic ob/ob and db/db mice fed a standard or high-calorie diet

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dc.contributor.author Nasser, Selim
dc.contributor.author Trak-Smayra, Viviane
dc.contributor.author Paradis, Valerie
dc.contributor.author Massart, Julie
dc.contributor.author Jebara, Victor
dc.contributor.author Fromenty, Bernard
dc.date.accessioned 2017-02-02T08:47:12Z
dc.date.available 2017-02-02T08:47:12Z
dc.date.copyright 2011 en_US
dc.date.issued 2017-02-02
dc.identifier.issn 0959-9673 en_US
dc.identifier.uri http://hdl.handle.net/10725/5150
dc.description.abstract Non-alcoholic fatty liver disease (NAFLD) is one of the commonest liver diseases in Western countries. Although leptin deficient ob/ob and db/db mice are frequently used as murine models of NAFLD, an exhaustive characterization of their hepatic lesions has not been reported to date, particularly under calorie overconsumption. Thus, liver lesions were characterized in 78 ob/ob and db/db mice fed either a standard or high-calorie (HC) diet, for one or three months. Steatosis, necroinflammation, apoptosis and fibrosis were assessed and the NAFLD activity score (NAS) was calculated. Steatosis was milder in db/db mice compared to ob/ob mice and was more frequently microvesicular. Although necroinflammation was usually mild in both genotypes, it was aggravated in db/db mice after one month of calorie overconsumption. Apoptosis was observed in db/db mice whereas it was only detected in ob/ob mice after HC feeding. Increased apoptosis was frequently associated with microvesicular steatosis. In db/db mice fed the HC diet for three months, fibrosis was aggravated while steatosis, necroinflammation and apoptosis tended to alleviate. This was associated with increased plasma β-hydroxybutyrate suggesting an adaptive stimulation of hepatic mitochondrial fatty acid oxidation (FAO). Nevertheless, one-third of these db/db mice had steatohepatitis (NAS ≥ 5), whereas none of the ob/ob mice developed non-alcoholic steatohepatitis under the same conditions. Steatosis, necroinflammation, apoptosis and fibrosis are modulated by calorie overconsumption in the context of leptin deficiency. Association between apoptosis and microvesicular steatosis in obese mice suggests common mitochondrial abnormalities. Enhanced hepatic FAO in db/db mice is associated with fibrosis aggravation. en_US
dc.language.iso en en_US
dc.title Pathology of the liver in obese and diabetic ob/ob and db/db mice fed a standard or high-calorie diet en_US
dc.type Article en_US
dc.description.version Published en_US
dc.author.school SOM en_US
dc.author.idnumber 200804624 en_US
dc.author.department N/A en_US
dc.description.embargo N/A en_US
dc.relation.journal International Journal of Experimental Pathology en_US
dc.journal.volume 92 en_US
dc.journal.issue 6 en_US
dc.article.pages 413-421 en_US
dc.identifier.doi http://dx.doi.org/10.1111/j.1365-2613.2011.00793.x en_US
dc.identifier.ctation Trak‐Smayra, V., Paradis, V., Massart, J., Nasser, S., Jebara, V., & Fromenty, B. (2011). Pathology of the liver in obese and diabetic ob/ob and db/db mice fed a standard or high‐calorie diet. International journal of experimental pathology, 92(6), 413-421. en_US
dc.author.email selim.nasser@lau.edu.lb en_US
dc.identifier.tou http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php en_US
dc.identifier.url http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2613.2011.00793.x/full en_US
dc.author.affiliation Lebanese American University en_US

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