Different PPARs agonists modify nuclear lipid metabolism in rat cerebellum

GAVEGLIO, V.L.; GIUSTO, N.M.; PASQUARÉ, S.J.

Ciudad Autónoma de Buenos Aires

Congreso; XLIX Reunión Anual SAIB; 2013

Previous research from our lab demonstrated an active phosphatidic acid (PA) metabolism in isolated nuclei from rat cerebellum. We detected and characterized several enzymatic activities related to its metabolism, such as lipid phosphate phosphatase (LPP), diacylglicerol lipase (DAGL), monoacylglycerol lipase (MAGL), phospholipase A (PLA) and lysophosphate phosphatase (LPAPase). Interestingly, we also showed that they are differently regulated by trans-retinoic acid through an unknown non-genomic mechanism. Thus, in this work we study the modulation of these enzymatic activities by different fatty acids (FA) and their derivatives which could interact with nuclear receptors, such as peroxisome proliferator-activated receptors (PPARs). To this end, adult rat cerebellums were homogenized and highly purified nuclei were isolated by sucrose-density ultracentrifugation. Using the respective radiolabelled substrates co-incubated with these agonists, we observed that arachidonic acid and docosahexaenoic acid stimulate DAGL activity by 80%. PGE2 also produced a stimulatory effect on this activity but to a major extent (128%) while slightly diminished LPP activity (19%). Taken together, these results demonstrate a lipid metabolism regulated by FA and related molecules in rat cerebellum nuclei that could be involved in gene expression and differentiation, apoptosis or inflammation processes.