Neuronal ceroid lipofuscinosis (NCL) is a relatively common group of inherited neurodegenerative disorders characterised by the accumulation of autofluorescent lipopigments (ceroid) similar to lipofuscin. Because of this property, studies have concentrated on fatty acid metabolism and lipid peroxidation.In the present study, the fatty acid composition of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) and the molecular species compositions of diacylglycerophosphocholine (diacyl GPC), diacylglycerophosphoethanolamine (diacyl GPE) and alkenylacyl GPE (plasmalogens) were investigated in cultured skin fibroblasts from three patients with a confirmed diagnosis of the late infantile form of the disease (LINCL, CLN2) and three healthy age-matched controls.Relatively minor differences in the fatty acid compositions of PC and PE were observed between patients and controls. However, dimethyl acetals of plasmalogens were found to be 40% higher in the patients compared to in the controls. Control and LINCL fibroblasts displayed only slight differences in the molecular compositions of diacyl GPE and diacyl GPC. In contrast, compared with normal cells, LINCL fibroblasts had higher levels of alkenylacyl GPE species containing both 18 : 1 and polyunsaturated fatty acids, but lower levels of species with 16 : 0 or 18 : 0 in the sn-1 position.The molecular composition of PC and PE subclasses in skin fibroblasts of healthy subjects and patients suffering from LINCL is here described for the first time. While few differences are noticeable in the fatty acid composition of PC and PE and the molecular species distribution of diacylGPC and diacylGPE, the alkenylacyl GPE (or ethanolamine plasmalogens) were found to differ significantly between patients and healthy controls.
Fatty acids have been shown to be selectively mobilized from rat white fat-cells, whatever the dietary manipulations. For convenience, fatty acids have been classified as being highly, weakly and moderately mobilizable. The aim of this study was to examine whether the selective mobilization of fatty acids can be explained, even partly, by their positional distribution in adipose-tissue triacylglycerols (TAG) via the known specificity of hormone-sensitive lipase for the sn-1 and sn-3 positions. Adipose tissue was dietarily manipulated in order to obtain a wide spectrum of fatty acids, including large amounts of either very-long-chain polyunsaturated fatty acids (VLC-PUFA) or very-long-chain monounsaturated fatty acids (VLC-MUFA). The determination of fatty acid distribution in adipose tissue TAG was based on random formation of 1,2-diacyl-rac-glycerols by Grignard degradation, followed by synthesis of phosphatidic acids and hydrolysis in the sn-2 position by phospholipase A2. Regardless of the fatty acid composition and location of fat depots, highly (e.g. 18:4n-3 and some of the VLC-PUFA) and weakly (e.g. VLC-MUFA) mobilizable fatty acids were located mainly in the outer (sn-1 and sn-3) positions of the glycerol moiety (79.5% and 92.5% on average, respectively). Other fatty acids, which are rather moderately mobilizable, were more randomly distributed. We conclude that the selective mobilization of white-fat-cell fatty acids is not based on their positional distribution in TAG.
Fatty acids of marine origin have been shown to affect blood coagulation in the rat. In an attempt to gain insight into the mechanisms of this phenomenon, we studied the effects of dietary linseed and fish oils on the liver antioxidant status and plasma coagulation parameters in rats on a time-course basis. Dietary enrichment in eicosapentaenoic and docosahexaenoic acids resulted in strong hypocoagulation after only 1 week and a concomitant increase in liver lipid peroxidation and tocopherolquinone content. Enrichment in linolenic acid induced similar increases in lipid peroxidation and tocopherol catabolism but negligible alteration of coagulation. A significant correlation between plasma factor II coagulant activity and liver tocopherolquinone was found in fish oil- but not in linseed oil-fed rats. Although ingestion of tocopherolquinone led to high levels of this compound in the liver, it had only marginal effects on coagulation factors. Thus, it seems unlikely that this vitamin E metabolite could be involved in the lowering of vitamin K-dependent clotting factors through inhibition of gamma-glutamylcarboxylase. Rather, our results indicate that the effects of the n-3 fatty acids of fish oil on vitamin K-dependent coagulation factors are specific and independent of liver tocopherolquinone levels.
