Nuclear lipid metabolism is differently regulated by polyunsaturated fatty acids during aging

Abstract

Former studies from our lab demonstrated an active nuclear lipid metabolism in central nervous system that is modified by aging. We detected several nuclear enzymatic activities related to glycerolipid metabolism, such as lipid phosphate phosphatase (LPP), diacylglycerol lipase (DAGL), monoacylglycerol lipase (MAGL), phospholipase A (PLA) and lysophosphate phosphatase (LPAPase). Interestingly, we also observed that they could be regulated by retinoic acid and polyunsaturated fatty acids (PUFA) through an unknown non-genomic mechanism in adult nuclei. Therefore, the aim of this work was to study the modulation of these enzymatic activities by arachidonic acid (AA) and docosahexaenoic acid (DHA) in nuclei from cerebellum of aged rats. To this end, rat cerebellums (28 mo) were homogenized and highly purified nuclei were isolated by sucrose-density ultracentrifugation. Using the respective radiolabelled substrates co-incubated with these PUFA, we observed that AA and DHA promote a major DAG availability by increasing and decreasing LPPs and DAGL activity, respectively. A minor MAG availability was also observed due to a diminution on PLA and LPAPase activities. These results demonstrate a different PUFA-regulated lipid metabolism in aged nuclei with respect to adults which could be involved in signaling events related to the epigenetic changes during aging.