n-3 Polyunsaturated fatty acids in animal models with neuroinflammation

Neuroinflammation is present in the majority of acute and chronic neurological disorders. Excess or prolonged inflammation in the brain is thought to exacerbate neuronal damage and loss. Identifying modulators of neuroinflammation is an active area of study since it may lead to novel therapies. Omega-3 polyunsaturated fatty acids (n-3 PUFA) are anti-inflammatory in many non-neural tissues; their role in neuroinflammation is less studied. This review summarizes the relationship between n-3 PUFA and brain inflammation in animal models of brain injury and aging. Evidence by and large shows protective effects of n-3 PUFA in models of sickness behavior, stroke, aging, depression, Parkinson's disease, diabetes, and cytokine- and irradiation-induced cognitive impairments. However, rigorous studies that test the direct effects of n-3 PUFA in neuroinflammation in vivo are lacking. Future research in this area is necessary to determine if, and if so which, n-3 PUFA directly target brain inflammatory pathways. n-3 PUFA bioactive metabolites may provide novel therapeutic targets for neurological disorders with a neuroinflammatory component.     

Transfer of maternal plasma free fatty acids into the rat fetus.

The amount of maternal plasma free fatty acids passing to the fetus has been determined to be 0.09 mumoles fatty acids per min per each litter. Taking account of the increase of the total fetal fatty acid pool due to the fetal growth (0.2 mumoles fatty acids per min for each litter) we conclude that the maternal circulation is the source of about half of fetal fatty acids on day 21 of pregnancy.     

Age-associated changes in rat plasma lipids, platelet fatty acids and prostacyclin release

The effect of age on plasma lipids, platelet fatty acids and prostacyclin release was studied in the rat. The contents of arachidonic acid, cholesterol, bile acids and free fatty acids in the plasma of aged rats (15 months old) were higher than those of young rats (3 months old). No significant differences in fatty acid composition of platelet lipids and release of prostacyclin from aortas between young and aged rats were observed. The data suggest that plasma lipids may play a more important role in the development of cardiovascular disease with increasing age than prostaglandins do.     

Interaction of fatty acids with recombinant rat intestinal and liver fatty acid-binding proteins

Intestinal enterocytes contain two homologous fatty acid-binding proteins, intestinal fatty acid-binding protein (I-FABP)2 and liver fatty acid-binding protein (L-FABP). Since the functional basis for this multiplicity is not known, the fatty acid-binding specificity of recombinant forms of both rat I-FABP and rat L-FABP was examined. A systematic comparative analysis of the 18 carbon chain length fatty acid binding parameters, using both radiolabeled (stearic, oleic, and linoleic) and fluorescent (trans-parinaric and cis-parinaric) fatty acids, was undertaken. Results obtained with a classical Lipidex-1000 binding assay, which requires separation of bound from free fatty acid, were confirmed with a fluorescent fatty acid-binding assay not requiring separation of bound and unbound ligand. Depending on the nature of the fatty acid ligand, I-FABP bound fatty acid had dissociation constants between 0.2 and 3.1 microM and a consistent 1:1 molar ratio. The dissociation constants for L-FABP bound fatty acids ranged between 0.9 and 2.6 microM and the protein bound up to 2 mol fatty acid per mole of protein. Both fatty acid-binding proteins exhibited relatively higher affinity for unsaturated fatty acids as compared to saturated fatty acids of the same chain length. cis-Parinaric acid or trans-parinaric acid (each containing four double bonds) bound to L-FABP and I-FABP were displaced in a competitive manner by non-fluorescent fatty acid. Hill plots of the binding of cis- and trans- parinaric acid to L-FABP showed that the binding affinities of the two sites were very similar and did not exhibit cooperativity. The lack of fluorescence self-quenching upon binding 2 mol of either trans- or cis-parinaric acid/mol L-FABP is consistent with the presence of two binding sites with dissimilar orientation in the L-FABP. Thus, the difference in binding capacity between I-FABP and L-FABP predicts a structurally different binding site or sites.     

Automatic titration of plasma fatty acids by photocolorimetry

A photocolorimeter for rapid automatic titration of free fatty acids is described. The solvents, absolute ethanol and hexane, form a single-phase titration mixture containing Nile blue indicator. The titrant, NaOH in 60% ethanol, is delivered by a motor-driven microsyringe; as alkali is added and the titration mixture turns pink, the intensity of light reaching a photocell through a 600 m micro interference filter increases. Increased current is generated until at a preselected number of microamperes a cut-off switch is activated which halts the drive motor. Titrations of FFA in the range 150-1500 micro eq/liter of palmitic acid standard are accomplished in approximately 1 min with a standard error of the mean of +/-1.3-6.5 micro eq/liter. The titration end point is independent of the operator. The solutions are stable and the daily titration blank and calibration remain constant. The procedure, therefore, is relatively simple and is quickly set up for routine determinations.     

Effects of cholestyramine feeding on tissue lipase activities and plasma fatty acids in the pregnant rat

Rats fed a non-absorbable bile acid binding resin (cholestyramine) throughout gestation had decreased activities of adipose tissue lipoprotein lipase (LPL), hepatic triacylglycerol lipase and a heparin-releasable placental lipase distinct from LPL, when assayed at near-term gestation. The fetal plasma and liver triacylglycerol concentrations were not altered. The fetal liver total lipid and plasma triacylglycerol, however, had reduced levels of n-6 and n-3 series fatty acids, suggesting decreased availability of maternal dietary-derived essential fatty acids. These studies suggest that cholestyramine feeding may alter triacylglycerol flux and the quantity or type of maternal fatty acids available for placental transfer. The resin has application for in vivo study of the effects of maternal lipid transfer on the regulation of fetal hepatic lipid synthesis.     

The significance of plasma triacylglycerols in metabolism of free fatty acids and triacylglycerols in rat skeletal muscles

The continuous uptake of plasma triacylglycerols has been shown to be necessary to maintain the stable resting concentration of free fatty acids and triacylglycerols only in a muscle composed of fast--twitch oxidative glycolytic fibres.     

The mobilization of free fatty acids in relation to adipose tissue triglyceride fatty acids in the rat

Three diets, consisting respectively of formulations high in oleic and stearic acid, linolenic acid, and lauric acid, were fed to rats until the adipose tissue TGFA largely reflected the dietary pattern of fatty acids. The composition of the serum FFA under basal conditions and following noradrenaline-stimulated lipolysis, were examined in relation to the respective adipose tissue TGFA. It was found in both in vivo and in vitro studies that lauric acid appeared to be less easily mobilized than longer chain acids. The in vitro studies indicated that this could not be explained either by positional preference of the shorter chain acids for the alpha-position of esterification or by increased reesterification of the shorter chain acids. The possibility remains that the difference is due to some specificity of tissue lipases for certain ester linkages.     

Quantitative extraction and determination of nonesterified fatty acids in plasma

A method is described for the determination of nonesterified fatty acids in plasma. Extraction is at least 98% efficient, and losses during subsequent stages are corrected for by the use of an internal radioactive standard. The method is suitable for reference purposes rather than for routine determinations. Higher values are obtained than by other methods of analysis, and it is suggested that some plasma fatty acids remain protein-bound after normal methods of extraction.     

Diurnal rhythms in rat plasma amino acids

To obtain detailed data on the diurnal rhythm in rat plasma amino acids, groups of rats were killed every two hours during 24 hours and the amino acids in plasma were measured. By using such a short interval between the blood samples, it was possible to reveal differences in rhythmicity between the various amino acids, more detailed than those previously described. Furthermore, it was found that those large neutral amino acids (LNAA) which compete with each other for the carrier mediated transport from plasma into the brain demonstrated different rhythms, whereby also the relation between these competing amino acids varied during the day. This finding might have implications for the transport of the various LNAAs into the brain, and secondarily also for the synthesis of the monoaminergic neurotransmitters in the neurons, for which the LNAAs tyrosine and tryptophan serve as precursors.