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dc.contributor.authorStanimirovic, Julijana
dc.contributor.authorObradovic, Milan
dc.contributor.authorJovanovic, Aleksandra
dc.contributor.authorSudar-Milovanovic, Emina
dc.contributor.authorZafirovic, Sonja
dc.contributor.authorPitt, Samantha Jane
dc.contributor.authorStewart, Alan James
dc.contributor.authorIsenovic, Esma R
dc.identifier.citationStanimirovic , J , Obradovic , M , Jovanovic , A , Sudar-Milovanovic , E , Zafirovic , S , Pitt , S J , Stewart , A J & Isenovic , E R 2016 , ' A high fat diet induces sex-specific differences in hepatic lipid metabolism and nitrite/nitrate in rats ' , Nitric Oxide , vol. 54 , pp. 51-59 .
dc.identifier.otherORCID: /0000-0003-4580-1840/work/60195814
dc.identifier.otherORCID: /0000-0003-2257-1595/work/60196235
dc.descriptionThis work is supported by the grants No.173033 and III41028 from the Ministry of Science, Republic of Serbia.en
dc.description.abstractMen and women differ substantially in regard to the severity of insulin resistance (IR) but the underlying mechanism(s) of how this occurs is poorly characterized. We investigated whether a high fat (HF) diet resulted in sex-specific differences in nitrite/nitrate production and lipid metabolism and whether these variances may contribute to altered obesity-induced IR. Male and female Wistar rats were fed a standard laboratory diet or a HF diet for 10 weeks. The level of plasma nitrite/nitrate, as well as free fatty acid (FFA), in both plasma and liver lysates were assessed. The levels of inducible nitric oxide (NO) synthase (iNOS), p65 subunit of NFκB, total and phosphorylated forms of Akt, mTOR and PDK-1 in lysates, and the levels of glucose transporter 2 (Glut-2) and fatty acid translocase/cluster of differentiation 36 (FAT/CD36) in plasma membrane fractions of liver were assessed. HF-fed male rats exhibited a significant increase in plasma nitrite/nitrate, and hepatic FFA and FAT/CD36 levels compared with controls. They also displayed a relative decrease in iNOS and Glut-2 levels in the liver. Phosphorylation of Akt (at Ser473 and Thr308), mTOR and PDK-1 was also reduced. HF-fed female rats exhibited increased levels of NFκB-p65 in liver compared with controls, while levels of Glut-2, FAT/CD36 and Akt phosphorylation at Thr308 and PDK-1 were decreased. Our results reveal that altered lipid and glucose metabolism in obesity, lead to altered iNOS expression and nitrite/nitrate production. It is likely that this mechanism contributes to sex-specific differences in the development of IR.
dc.relation.ispartofNitric Oxideen
dc.subjectHigh fat dieten
dc.subjectSex differencesen
dc.subjectInsulin resistanceen
dc.subjectLiver metabolismen
dc.subjectRM Therapeutics. Pharmacologyen
dc.subjectSDG 3 - Good Health and Well-beingen
dc.titleA high fat diet induces sex-specific differences in hepatic lipid metabolism and nitrite/nitrate in ratsen
dc.typeJournal articleen
dc.contributor.institutionUniversity of St Andrews. School of Medicineen
dc.contributor.institutionUniversity of St Andrews. Institute of Behavioural and Neural Sciencesen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.description.statusPeer revieweden

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