BBB webinar: Knut Tomas Dalen
Lipid droplets and transgenic animals
Knut Tomas Dalen
Department of Nutrition and Norwegian Transgenic Center, Institute of Basic Medical Sciences, University of Oslo
To understand how lipid droplets (LDs) affect development of lipid-mediated diseases, the LD-group at the Department of Nutrition studies transcriptional regulation of LD proteins and metabolic consequences of disturbed LD storage. We have generated genetically altered mouse models lacking expression of Plin proteins. The five Plin proteins bind to the LD-surface and protect LDs against lipolytic enzymes degrading triacylglycerol (TAG) or cholesteryl ester (CE), but with variable efficiency. The LD-group performs systematic diet interventions in Plin-/- mice to dissect the role of each Plin in development of insulin resistance and hepatic steatosis.
The LD-group has demonstrated that some Plin proteins have a preference for either TAG-LDs or CE-LDs; resulting in unbalanced accumulation of neutral lipids when over-expressed. The group has further shown that mice lacking Plin2 have reduced LD content in liver and muscle. Cultured Plin2-/- myotubes store less TAG-LDs due to elevated lipolysis, with a shift in oxidation of glucose toward fatty acid oxidation. Additionally, Plin2-/- mice have enlarged adrenals due to elevated levels of CE-LDs in the adrenal cortex and accumulate lipid containing ceroid-like structures and high levels of phosphatidylglycerol lipid species with aging. Plin5 is expressed in organs with high mitochondrial content, such as heart and oxidative muscles (soleus). Plin5-/- mice store low levels of TAG-LDs in cardiomyocytes and have reduced heart function and increased mortality after myocardial ischemia in vivo, in contrast to increased tolerance to hypoxia in Plin5-/- cardiomyocytes cultured ex vivo. The above and unpublished observations show that improper storage of LDs affects development of lipid-mediated diseases.
The seminar will cover LD biology, with focus on the role of various Plin proteins, and provide a description of transgenic services provided by the Norwegian Transgenic Center.
Chairperson: Donald Gullberg, Department of Biomedicine