title: Adipose triglyceride lipase affects triacylglycerol metabolism at brain barriers.
abstract: 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 brain-CSF interface, the blood-CSF barrier, and the blood-brain barrier.
authors.affiliation: Institute of Pathophysiology and Immunology, Medical University of Graz, Graz, Austria.
authors.forename: Karoline
authors.initials: K
authors.lastname: Etschmaier
authors.forename: Tatjana
authors.initials: T
authors.lastname: Becker
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Eichmann
authors.forename: Cornelia
authors.initials: C
authors.lastname: Schweinzer
authors.forename: Monika
authors.initials: M
authors.lastname: Scholler
authors.forename: Carmen
authors.initials: C
authors.lastname: Tam-Amersdorfer
authors.forename: Michael
authors.initials: M
authors.lastname: Poeckl
authors.forename: Rufina
authors.initials: R
authors.lastname: Schuligoi
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kober
authors.forename: Anil Paul
authors.initials: AP
authors.lastname: Chirackal Manavalan
authors.forename: Gerald N
authors.initials: GN
authors.lastname: Rechberger
authors.forename: Ingo E
authors.initials: IE
authors.lastname: Streith
authors.forename: Rudolf
authors.initials: R
authors.lastname: Zechner
authors.forename: Robert
authors.initials: R
authors.lastname: Zimmermann
authors.forename: Ute
authors.initials: U
authors.lastname: Panzenboeck
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000201:enzymology* / Q000378:metabolism; D001921:Brain / Q000201:enzymology* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D008049:Lipase / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D050356:Lipid Metabolism / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014280:Triglycerides / Q000378:metabolism; D000217:Acyltransferases
chemical_list: D008049:Lipase; D014280:Triglycerides; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases