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dc.identifier.citationSlettås, Marit Opsahl. The Modulation of Hepatic Lipid Homeostasis by the Anti-inflammatory Interleukin-10. Masteroppgave, University of Oslo, 2008en_US
dc.description.abstractFor humans it is crucial to control lipid homeostasis to avoid development of metabolic disorders. Dyslipidemia is a considerable risk factor for development of cardiovascular and liver diseases, such as non-alcoholic fatty liver disease (NAFLD). Infection and inflammation induce the acute phase response (APR), leading to multiple alternations in lipid and lipoprotein metabolism, mediated by changed cytokine production, especially tumor necrosis factor (TNF)-a, interleukin (IL)-1 and IL-6. Another cytokine IL-10 has anti-atheromatous and anti-inflammatory effects, and it has been postulated that IL-10 has gene therapeutic potential. However, the effect of IL-10 on liver and its metabolic functions are still unclear. In the present study, we investigated whether IL-10 could modulate lipid homeostasis in TNF-a- and IL-6-stimulated hepatocytes. We demonstrated that IL-6 increased expression of genes involved in hepatic fatty acid (FA) synthesis [SREBP1a, FAS], FA oxidation [PPARa, CPT1a, CPT2], FA storage [ADRP] and cholesterol secretion into circulation [ABCA1], whereas genes involved in cholesterol secretion into bile [ABCG5, ABCG8] were decreased. Moreover, TNF-a decreased genes involved in hepatic FA synthesis [LXRa, SREBP1a], FA oxidation [PPARa, CPT1a] and bile acid synthesis [CYP7A1], while FA storage [ADRP] was increased. In addition, IL-6 and TNF-a increased protein levels of fibrinogen and IL-8, respectively. IL-10 amplified the upregulation of PPARa, CPT1a, CPT2 and ABCA1 gene expressions mediated by IL-6 and ADRP gene expressions induced by TNF-a. IL-10 increased cholesterol secretion into circulation [ABCA1] and decreased bile acid synthesis [CYP7A1], and IL-10 appeared to increase cholesterol secretion into bile [ABCG5 and ABCG8]. The present findings indicate that IL-10 mainly presents its anti-inflammatory effect in the vessel wall, as described in the literature, rather than changing lipid metabolism in the liver.nor
dc.titleThe Modulation of Hepatic Lipid Homeostasis by the Anti-inflammatory Interleukin-10en_US
dc.typeMaster thesisen_US
dc.creator.authorSlettås, Marit Opsahlen_US
dc.identifier.bibliographiccitationinfo:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft.au=Slettås, Marit Opsahl&rft.title=The Modulation of Hepatic Lipid Homeostasis by the Anti-inflammatory Interleukin-10&rft.inst=University of Oslo&rft.date=2008&rft.degree=Masteroppgaveen_US
dc.contributor.supervisorBente Halvorsen, Arild Rustanen_US

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