Diet induced altered fatty acid composition and the activation of their metabolizing enzymes in mice

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dc.contributor.advisorRühl, Ralph
dc.contributor.authorWeiss-Hersh, Kathrin
dc.contributor.authorvariantWeiss, Kathrin
dc.contributor.departmentMolekuláris sejt- és immunbiológia doktori iskolahu
dc.date.accessioned2018-03-13T09:20:42Z
dc.date.available2018-03-13T09:20:42Z
dc.date.created2017hu_HU
dc.date.defended2018-04-09
dc.description.abstractDietary fat provides FAs incorporated into PLs forming cellular membranes. These membranes are constantly renewed and the composition of FAs aligns according to the provided dietary fat. Influences on membrane PL FA composition were investigated in this thesis. In vivo studies in mice have been performed investigating the effect of different types of dietary fat, different amounts of sunflower oil combined with vitamin A and regulation by activated NHRs on PLs and cellular membrane FA profile. Most important findings of this thesis were that MUFA and SAFA content in PLs is strictly controlled by their metabolizing enzymes SCD1 and ELOVL6. Especially alteration of SCD1 hepatic gene expression by dietary fat altered the PLs profile of its metabolic products accordingly. The SCD1 FA ratio 18:1n9/18:0 was found to be more reliable as “desaturase index” within all conducted studies. Most surprisingly margarine diet was the strongest inducer of SCD1, it was even more effective than coconut fat diet high in SAFA. Furthermore the inductive effect of dietary vitamin A on hepatic gene expression of SCD1 and ELOVL6 was abolished if diet was combined with n6-PUFA rich sunflower oil. Sunflower oil supplemented diet suppressed SCD1 and ELOVL6 gene expression dose dependently. This assumes that nutrients might interfere with each other with unexpected outcome. ELOVL6 activity was most reliable represented by the FA ratio 18:0/16:0. On the contrary to MUFA and SAFA profile in PLs PUFAs in PLs were more but not totally dependent on available dietary PUFAs. Fish oil enriched diet suppresses the hepatic gene expression of main PUFA metabolizing enzymes FADS1, FADS2 and ELOVL5 which was reflected in reduced metabolic activity. This resulted partially in less metabolic products measured in FA profile of PLs. Repressed gene expression could be associated with reliable FA ratios representing enzymatic activity for 22:6n3/22:5n3 FADS2. PUFAs in PLs profiles are more likely to derive directly from diet, but might be adjustable by PUFA enzyme metabolism. The results of this thesis suggest further that inhibition of hepatic gene expression of fat metabolizing enzymes by n3-PUFA enriched diet is caused by reduces activity of RXR. RXR is a heterodimer forming NHR which can be activated by isoforms of vitamin A. CYP26A1 catabolizes active vitamin A derived RXR ligands into inactive metabolites. Induction of CYP26a1 by fish oil supplemented diet decreases the availability of vitamin A and less RXR is activated.hu_HU
dc.description.correctorde
dc.format.extent79hu_HU
dc.identifier.urihttp://hdl.handle.net/2437/248644
dc.language.isoenhu_HU
dc.subjectStearoyl-CoA desaturasehu_HU
dc.subjectElongase
dc.subjectFatty acid desaturase
dc.subjectNuclear Hormone Receptors
dc.subjectPhospholipids
dc.subjectPhosphatidylethanolamine
dc.subjectPhosphatidylcholine
dc.subjectLysophosphatidylcholine
dc.subjectESI-MS/MS
dc.subjectmonounsaturated fatty acid
dc.subjectsaturated fatty acid
dc.subjectpolyunsaturated fatty acid
dc.subject.disciplineElméleti orvostudományokhu
dc.subject.sciencefieldOrvostudományokhu
dc.titleDiet induced altered fatty acid composition and the activation of their metabolizing enzymes in micehu_HU
dc.title.translatedTáplálkozás okozta zsírsav összetétel változás, illetve metabolikus enzimek aktiválásának vizsgálata egérbenhu_HU
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