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Questionnaires, biological samplings and measurements (DOC 43 kb)

The CRC-NORDIET intervention program (DOC 42 kb)

Detailed list of foods and drinks with high contents of redox-active compounds and/or antioxidative effects (DOCX 22 kb)

Lipid droplet storage proteins (LSDPs) associate with lipid droplets and are involved in the molecular processes of deposition and catabolism of stored lipids in the cells. These proteins differ in tissue distribution, binding affinity to lipid storage droplets, protein stability and transcriptional regulation. Due to these differences, they are believed to have evolved to fine tune fatty acid metabolism according to the particular needs of various tissues. Recent knowledge reveals that these proteins are transcriptionally regulated by Peroxisome Proliferator-Activated Receptors (PPAR). In this thesis I have focused on the newly discovered protein, lipid storage droplet protein 5 (LSDP5), and the transcriptional regulation of this protein. Nebbs group has previously demonstrated in animal studies that LSDP5 is transcriptionally regulated by PPARá in liver. However, it has been difficult to prove through transfection studies that this regulation is mediated through a PPARá responsive DR1 element (PPRE). The main objective for this thesis was thus to establish whether there is a functional PPRE located in the LSDP5 promoter. Furthermore, the aims were to examine whether the transcriptional regulation of LSDP5 is affected by additional regulatory factors; the transcription factor estrogen-related receptor á (ERRá) and the coactivator PPARã coactivator-1á (PGC-1á). In this study it was confirmed that LSDP5 contains a functional PPRE, located in the -2077base pairs (bp) to -2064bp upstream region in the LSDP5 gene. Furthermore, it was demonstrated that the PPARá mediated transcriptional regulation of LSDP5 is dependent on PGC-1á. PGC-1á enhanced the transcriptional activity in the LSDP5 gene remarkably. ERRá repressed the expression of LSDP5. We observed that the presence of ERRá reduced the enhancing effect of PGC-1á on LSDP5 induction. Taken together, my data and the previously published data in our group confirm that LSDP5 is a PPARá target gene. Furthermore, our findings provide new aspects in the regulation of LSDP5, regarding the role PGC-1á and ERRá.