Regulation of lipid metabolism in macrophages by long-chain metabolites of α-tocopherol

With only two years away from the 100th anniversary of the discovery of vitamin E as an essential nutrient in 1922, we have still more questions than answers concerning its significance for human health. During the past hundred years, vitamin E research was characterized by great hopes but also bitter disappointments, which finally led to a strong decline of interest in this research area. However, vitamin E research is currently experiencing a scientific renaissance, which is among others attributed to the unrevealing of vitamin E metabolism in humans and to the elucidation of biological functions of the newly formed metabolites. Since their initial determination in human serum, especially the long-chain metabolites (LCMs), i.e. the first metabolites formed during the hepatic degradation of vitamin E, appeared as a class of molecules with putative relevance in the human body. Driven by a small community of ambitious scientist, research on these compounds has made great progress over the last decade, leading to the establishment of the LCMs as an acknowledged area of vitamin E research. As one of the founding members of the LCM community, the work of our group is predominantly focused on the advance of this new and promising field of vitamin E research. Hence, the ten manuscripts included in this thesis also contribute to the progress of key areas in the field of LCM research, i.e. elucidation of biological functions, identification of signaling pathways and the comparison of LCM functionality with their vitamin precursors. Despite of this great progress on fundamental areas of LCM functionality, their exact modes of action as well as their significance for human health are still a puzzle waiting to be solved. Especially the lack of data on LCM physiology in a living organism represent a great limitation of current and the major challenge of future investigations.



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