Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Etschmaier, K.
Adipose triglyceride lipase (ATGL) affects triacylglycerol metabolism at brain barriers
[ Dissertation ] Medical University of Graz; 2011. pp. 86
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- Autor*innen der Med Uni Graz:
- Etschmaier Karoline
- Betreuer*innen:
- Panzenboeck Ute
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- Abstract:
- The discovery of adipose triglyceride lipase (ATGL) as the rate limiting enzyme in the initial step of triacylglycerol (TAG) catabolism in adipose tissue has shed new light on the mechanisms of lipolysis of storage lipids. Lipolysis of storage lipids is characterized by the breakdown of triacylglycerols (TAG) to free fatty acids (FFA) and glycerol in a three-step enzymatic process. The major lipases involved are adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL) and monoglycerol lipase (MGL). Except for MGL, which is an important regulatory enzyme of the endocannabinoid system, currently little is known about the role of intracellular neutral lipid (NL) lipases in the brain. In this study, we investigated the effects of ATGL and HSL deficiency on brain lipid metabolism using established knock-out mouse models (ATGL-ko, HSL-ko). We mainly focused on ATGL and could detect a moderate decrease in TAG hydrolase activity in ATGL-ko versus wildtype (WT) brain tissue. This 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. As expected, HSL in the brain is of importance for diacylglycerol (DAG) catabolism, whereas no influence of the lacking enzyme on phospholipid (PL) levels was found. However, a moderately increased accumulation of NL in droplets in blood vessels and choroid plexus ependymal cells detected in HSL-ko brains as compared to the WT, indicates that lack of HSL might reduce or slow down the TAG breakdown in these cells. Our studies imply that ATGL is involved in brain fatty acid metabolism, particularly in regions mediating transport- and exchange processes: the brain-cerebrospinal fluid (CSF) interface, the blood-CSF barrier (BCSFB), and the blood-brain barrier (BBB).