{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:50:39Z","timestamp":1791406239986,"version":"4.3.3"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":792,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>The global prevalence of obesity-induced liver disease (nonalcoholic fatty liver disease; NAFLD) is rising. Suggested causes include a role for <jats:italic toggle=\"yes\">in utero<\/jats:italic> influences of maternal obesity compounded by the availability of energy-dense foods throughout postnatal life. Using a physiologically relevant model, we investigated the role of the innate immune system in liver injury induced by maternal obesity followed by a postnatal obesogenic diet. Female C57BL\/6J mice were fed a standard or obesogenic diet before and throughout pregnancy and during lactation. Female offspring were weaned onto a standard or obesogenic diet at 3 weeks postpartum. Biochemical and histological indicators of dysmetabolism, NAFLD and fibrosis, analysis of profibrotic pathways, liver innate immune cells, and reactive oxygen species (ROS) were investigated at 3, 6, and 12 months. Female offspring exposed to a postweaning obesogenic diet (OffCon-OD) demonstrated evidence of liver injury, which was exacerbated by previous exposure to maternal obesity (OffOb-OD), as demonstrated by raised alanine aminotransferase, hepatic triglycerides, and hepatic expression of interleukin (IL)-6, tumor necrosis factor alpha, transforming growth factor beta, alpha smooth muscle actin, and collagen (<jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 0.01). Histological evidence of hepatosteatosis and a more-robust NAFLD phenotype with hepatic fibrosis was observed at 12 months in OffOb-OD. A role for the innate immune system was indicated by increased Kupffer cell numbers with impaired phagocytic function and raised ROS synthesis (<jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 0.01), together with reduced natural killer T cells and raised interleukin (IL)-12 and IL-18. <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> Maternal obesity in the context of a postnatal hypercalorific obesogenic diet aggressively programs offspring NAFLD associated with innate immune dysfunction, resulting in a comprehensive phenotype that accurately reflects the human disease. (HEPATOLOGY 2013)<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.26248","type":"journal-article","created":{"date-parts":[[2013,1,12]],"date-time":"2013-01-12T12:29:40Z","timestamp":1357993780000},"page":"128-138","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":136,"title":["Maternal obesity programs offspring nonalcoholic fatty liver disease by innate immune dysfunction in 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