Adipose triglyceride lipase affects triacylglycerol metabolism at brain barriers

作者：Etschmaier Karoline; Becker Tatjana; Eichmann Thomas O; Schweinzer Cornelia; Scholler Monika; Tam Amersdorfer Carmen; Poeckl Michael; Schuligoi Rufina; Kober Alexandra; Manavalan Anil Paul Chirackal; Rechberger Gerald N; Streith Ingo E; Zechner Rudolf; Zimmermann Robert; Panzenboeck Ute^*

来源：Journal of Neurochemistry, 2011, 119(5): 1016-1028.

DOI：10.1111/j.1471-4159.2011.07498.x

• ATGL
• PNPLA2
• brain barriers
• cerebral lipid metabolism
• fatty acid metabolism
• lipid droplets

Currently, little is known about the role of intracellular triacylglycerol (TAG) lipases in the brain. Adipose triglyceride lipase (ATGL) is encoded by the PNPLA2 gene and catalyzes the rate-limiting step of lipolysis. In this study, we investigated the effects of ATGL deficiency on brain lipid metabolism in vivo using an established knock-out mouse model (ATGL-ko). A moderate decrease in TAG hydrolase activity detected in ATGL-ko versus wild-type brain tissue was accompanied by a 14-fold increase in TAG levels and an altered composition of TAG-associated fatty acids in ATGL-ko brains. Oil Red O staining revealed a severe accumulation of neutral lipids associated to cerebrovascular cells and in distinct brain regions namely the ependymal cell layer and the choroid plexus along the ventricular system. In situ hybridization histochemistry identified ATGL mRNA expression in ependymal cells, the choroid plexus, pyramidal cells of the hippocampus, and the dentate gyrus. Our findings imply that ATGL is involved in brain fatty acid metabolism, particularly in regions mediating transport and exchange processes: the brainCSF interface, the bloodCSF barrier, and the bloodbrain barrier.

• 出版日期2011-12