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PI, Kratky

Role of intracellular lipid hydrolases in lipid and energy metabolism in placenta and fetus


The role of lipases in lipid metabolism and inflammation in the placenta and the fetus are incompletely understood. We have previously reported on lipase activities in human and murine placenta with extracellular lipases (lipoprotein lipase, endothelial lipase) being involved (1). The role of intracellular lipases in lipid and energy metabolism in placenta and fetus, however, is currently unknown. We hypothesize that loss of intracellular lipid hydrolases (e.g. adipose triglyceride lipase, hormone-sensitive lipase, monoglyceride lipase, α/β hydrolase-containing 6, lysosomal acid lipase) affects lipid and / or energy metabolism in the placenta and the fetus, thereby leading to alterations in cells (e. g. macrophages and endothelial cells) and placental tissues. The DP-iDP student will utilize knockout mouse models with loss of the above mentioned enzymes to investigate the impact of the respective enzymes on lipid and energy metabolism in the placenta and the fetus. The student will perform tracer experiments to elucidate fatty acid and glucose uptake in placenta and fetus of the respective mouse model fed chow and high-fat diet (to trigger type 2 diabetes and inflammation). In addition, he/she will isolate RNA and protein, perform transcriptomics analyses and real time PCR analyses to determine mRNA expression changes in particular pathways, analyze hydrolase activities, and perform lipid uptake and efflux experiments in trophoblasts and endothelial cells (GD). We expect that the results from this study will advance our understanding of how lipolysis and the consequences of metabolic disorders affect the pathogenesis of inflammatory pregnancy-related diseases.

1. Lindegaard ML, Olivecrona G, Christoffersen C, Kratky D, Hannibal J, Petersen BL, Zechner R, Damm P, Nielsen LB. Endothelial and lipoprotein lipases in human and mouse placenta. J Lipid Res. 2005 Nov;46(11):2339-46. doi: 10.1194/jlr.M500277-JLR200.

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