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We evaluated control and HFD\u2010fed male and female FVB\/N mice, a strain well\u2010suited to transgenic analyses, for phenotypic, histological, and molecular markers related to control of glucose, lipids, and inflammation in serum, liver, and perigonadal white adipose tissues. Unlike many mouse models, HFD\u2010fed FVB\/N females gained more perigonadal and mesenteric fat mass and overall body weight than their male counterparts, with increased hepatic expression of lipogenic PPAR\u03b3 target genes (<jats:italic>Cd36<\/jats:italic>, <jats:italic>Fsp27<\/jats:italic>, and <jats:italic>Fsp27\u03b2<\/jats:italic>), oxidative stress genes and protein (<jats:italic>Nqo1<\/jats:italic> and CYP2E1), inflammatory gene (<jats:italic>Mip\u20102<\/jats:italic>), and the pro\u2010fibrotic gene <jats:italic>Pai\u20101<\/jats:italic>, along with increases in malondialdehyde and serum ALT levels. Further, inherent to females (independently of HFD), hepatic antioxidant heme oxygenase\u20101 (HMOX1, HO\u20101) protein levels were reduced compared to their male counterparts. In contrast, males may have been relatively protected from HFD\u2010induced oxidative stress and liver injury by elevated mRNA and protein levels of hepatic antioxidants BHMT and <jats:italic>Gpx2<\/jats:italic>, increased fatty acid oxidation genes in liver and adipocytes (Ppar\u03b4), despite disorganized and inflamed adipocytes. Thus, female FVB\/N mice offer a valuable preclinical, genetically malleable model that recapitulates many of the features of diet\u2010induced obesity and liver damage observed in human females.<\/jats:p>","DOI":"10.1002\/biof.2028","type":"journal-article","created":{"date-parts":[[2024,1,6]],"date-time":"2024-01-06T11:34:50Z","timestamp":1704540890000},"page":"572-591","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["High\u2010fat diet induced obesity promotes inflammation, oxidative stress, and hepatotoxicity in female <scp>FVB\/N<\/scp> mice"],"prefix":"10.1002","volume":"50","author":[{"given":"Malvin","family":"Ofosu\u2010Boateng","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences College of Pharmacy, The University of Tennessee Health Science Center  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1490-8748","authenticated-orcid":false,"given":"Fathima","family":"Shaik","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences College of Pharmacy, The University of Tennessee Health Science Center  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sora","family":"Choi","sequence":"additional","affiliation":[{"name":"Julius L. Chambers Biomedical Biotechnology Research Institute, North Carolina Central University  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick A.","family":"Ekuban","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences College of Pharmacy, The University of Tennessee Health Science Center  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidya H.","family":"Gebreyesus","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences College of Pharmacy, The University of Tennessee Health Science Center  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Twum","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences College of Pharmacy, The University of Tennessee Health Science Center  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel O.","family":"Nnamani","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences College of Pharmacy, The University of Tennessee Health Science Center  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan T.","family":"Yeyeodu","sequence":"additional","affiliation":[{"name":"Julius L. 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