Unsaturated Fatty Acids Esterified in 2‐Acyl‐1‐Lysophosphatidylcholine Bound to Albumin Are More Efficiently Taken up by the Young Rat Brain than the Unesterified Form

Thiès, Frank; Delachambre, Marie Claire; Bentéjac, Marc; Lagarde, Michel; Lecerf, Jean

doi:10.1111/j.1471-4159.1992.tb08353.x

Cited by 116 publications

(71 citation statements)

References 36 publications

(10 reference statements)

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“…Several studies on the effects of the differences of the DHA molecular types on the DHA level of the serum or brain have been reported. When the rats were injected with the labeled DHA into the tail vein, the lyso PC type of DHA was preferentially recovered in the brain over the unesterified type of DHA (29,30). In the studies of rats or mice fed the TG and PL types of DHA diets, the DHA levels in the brain and liver of the DHA-TG diet group were significantly higher than those of the DHA-PL diet group (31,32).…”

Section: Discussionmentioning

confidence: 97%

Effects of Dietary Docosahexaenoic Acid Connecting Phospholipids on the Learning Ability and Fatty Acid Composition of the Brain

Hiratsuka

Koizumi

Ooba³

et al. 2009

J Nutr Sci Vitaminol

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SummaryThe effects of dietary docosahexaenoic acid (DHA, C22:6 n -3) connecting phospholipids on the learning ability and fatty acid composition of the brain were investigated in hypercholesterolemic mice. ICR mice were subjected to a very low level of n -3 fatty acids through two generations. At 4 wk of age, the F 1 generation, n -3 fatty acid deficient male mice were provided with an experimental diet containing four kinds of lipids (safflower oil: Saf, DHA connecting triacylglycerols: DHA-TG, DHA connecting phospholipids: DHA-PL, soybean phospholipids: Soy-PL) for 5 wk. Another group of ICR mice were obtained and fed a commercial diet (CE-2, CLEA Japan, Inc.) as a control. The learning and memory abilities of the mice were evaluated by the modified avoidance procedure. The learning and memory ability level was significantly higher in mice fed the DHA-PL diet than in those fed the Saf and Soy-PL diets, and was the same level as the control. The DHA levels of phosphatidylethanolamine in the brain were significantly higher in the mice fed the two types of DHA-containing diets than in those fed the Saf and Soy-PL diets and was not significantly different between DHA-TG and DHA-PL. The dimethylacetal levels in the brain were significantly higher in the mice fed the DHA-PL diet than in those fed the Saf and DHA-TG diets. These results suggest that the dietary DHA connecting phospholipids have the effect of improving memory learning, and may be related to the both the DHA and plasmalogen levels in the brain.

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Section: Discussionmentioning

confidence: 97%

Effects of Dietary Docosahexaenoic Acid Connecting Phospholipids on the Learning Ability and Fatty Acid Composition of the Brain

Hiratsuka

Koizumi

Ooba³

et al. 2009

J Nutr Sci Vitaminol

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“…One consequence of the alteration in positional specificity is the formation of 20:4 lyso-PC or 22:6 lyso-PC in the lipoproteins. The studies of Thies et al (28,29) showed that 22:6 or 20:4 is taken up by the brain much more efficiently if present in lyso-PC form rather than in free fatty acid form. Thus, the formation of sn-2-22:6 lyso-PC by the LCAT reaction may be an effective form of delivery of this essential fatty acid to the brain, where it is known to play a critical role (30).…”

Section: Discussionmentioning

confidence: 99%

Evidence for altered positional specificity of LCAT in vivo

Subbaiah

Sowa

Davidson

2004

Journal of Lipid Research

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The percentage of saturated cholesteryl esters (CEs) synthesized by human LCAT is several times higher than expected from the sn -2 acyl composition of plasma phosphatidylcholine (PC), whereas the synthesis of 20:4 CE and 22:6 CE is much lower than expected. To explain these discrepancies, we proposed that LCAT transfers some saturated fatty acids from the sn -1 position of PC species that contain 20:4 or 22:6 at sn -2. The present studies provide in vivo evidence for this hypothesis. We determined the composition and synthesis of CE species in plasma of volunteers before and after a 6 week dietary supplementation with docosahexaenoic acid (22:6; DHA). In addition to an increase in the DHA content of all plasma lipids, there was a significant ( ؉ 12%; P Ͻ 0.005) increase of 16:0 CE, although there was no increase in 16:0 at sn -2 of PC. The increase of DHA in CE was much lower than its increase at sn -2 of PC. Most of the cholesteryl esters (CEs) in the lipoproteins of human plasma are derived from the action of LCAT (1). Although this enzyme has been shown to be specific for the sn-2 position of phosphatidylcholine (PC), the composition of the CEs in human plasma does not match that of the sn-2 acyl group (1-4). For example, although 16:0 constitutes only ‫ف‬ 2-3% of the PC sn-2 acyl groups, it accounts for 10-12% of plasma CE. On the other hand, although 20:4 constitutes ‫ف‬ 16% of the sn-2 acyl groups of PC, only ‫ف‬ 5% of the plasma CE is 20:4. Similarly, the concentration of 22:6 at sn-2 of PC ( ‫ف‬ 5%) is much higher than that in CE ( ‫ف‬ 0.4%). Although these discrepancies have been attributed to the preference of the enzyme for the PC substrates containing 16:0 at sn-2 (5), in vitro studies with synthetic substrates and isolated enzyme did not support this mechanism (6). Our studies on the use of PC species by LCAT in native plasma also showed that 16:0-16:0 PC, the major PC with 16:0 at sn -2, is not preferred over "average" PC in plasma. Based on our studies with synthetic PC substrates and isolated LCAT (7, 8), we proposed that human LCAT transfers significant amounts of sn-1 acyl group from the PC species containing 20:4 or 22:6 at the sn -2 position. This mechanism not only explains the synthesis of higher than expected percentages of saturated CE species but also accounts for the formation of lower than expected percentages of 20:4 and 22:6 CE. This alteration in positional specificity appears to be a function of the architecture of the enzyme's active site, because rat and mouse enzyme are not substantially affected by the presence of sn-2-20:4 PC (8) and because the human LCAT behaves like the mouse enzyme if its active site domain is replaced by the corresponding domain from mouse enzyme (4, 9).Although we have provided multiple lines of evidence for the altered positional specificity of human LCAT in vitro, there is no direct evidence that this occurs in vivo. Previous studies of the effects of fish oil feeding in humans (10) and nonhuman primates (11,12) reported an increase in the ap...

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“…LPC has been suggested as the major carrier of DHA to the brain tissues (Lagarde et al, 2001). Tracer studies revealed that labelled LPC-DHA and unesterified DHA injected into the blood of rat disappeared within 20 s and labelled LPC-DHA was recovered in different organs including the brain (Thies et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

“…These alterations indirectly affect signalling pathways and other physiological functions. Furthermore, the fatty acid on the sn-2 position of membrane PL could be cleaved by the action of phospholipase A 2 (PLA 2 ) to produce FFA and lyosphosphatidylcholine (LPC) which are both bioactive molecules (Thies et al, 1992). The released twenty carbon AA and EPA from the membrane phospholipids undergo cyclooxygenases (COX-1 and COX-2) and lipoxygenases-(LOX-5, LOX-12, LOX-15) catalysed oxidation to produce bioactive lipid intermediates and eicosanoids (Jump et al, 2012).…”

Section: Cardioprotective Effects Of N-3 Pufa By Altering Membrane Dymentioning

confidence: 99%

Lipid metabolism and the risk factors of cardiovascular disease: implication of dietary omega-3 polyunsaturated fatty acids

Balogun

2016

Appl. Physiol. Nutr. Metab.

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Cardiovascular disease (CVD) is a complicated and multifarious disease, and is the number cause of mortality worldwide. The pathogenesis of CVD is attributed to the interaction between genetics and environment. There are numerous data that support the cardioprotective properties of omega (n)-3 polyunsaturated fatty acids (PUFA); however, there are also controversial reports. Considering the reported sex and age differences in the pathophysiology of CVD and the metabolism of n-3 PUFA, it is imperative to consider these factors in the cardioprotective effects of n-3 PUFA. The main objective of the current thesis was to investigate the effects of n-3 PUFA on the risk factors of CVD such as dyslipidaemia and obesity, with particular focus on how sex, age and dose of n-3 PUFA affect lipid and lipoprotein metabolism. The set of experiments presented in this thesis was investigated using the C57BL/6 mouse strain which has been established as a mouse model of choice for the study of diet-induced pathological conditions of lipid and lipoprotein metabolism. Plasma concentrations of lipids and lipoproteins of mice offspring at weaning and 16 weeks postweaning were chosen as study outcomes to assess the sex, age and dose-specific effects of n-3 PUFA on markers of dyslipidaemia, a well-known risk factor of CVD. It was observed that a longer exposure to a postnatal diet high in n-3 PUFA increased plasma concentration of low-density lipoprotein cholesterol (LDL-c) in the offspring in a sex-specific manner; however, the profile of this increase was less atherogenic , as the high n-3 PUFA group had a lower plasma concentration of very small LDL-particles in both males and females. There was no effect of high n-3 PUFA diet observed on plasma concentration of highdensity lipoprotein cholesterol (HDL-c); however, the high n-3 PUFA group had a higher cholesterol efflux in the male offspring but not in female offspring, further demonstrating the effect of sex on cholesterol metabolism. Lipidomic analyses revealed that high n-3 PUFA diet iii led to higher hepatic and plasma concentrations of n-3 PUFA-containing bioactive lipids such a phosphatidylcholine, lysophosphatidylcholine and free fatty acids, which could positively influence pathways involved in cardioprotection. The effects of dietary n-3 PUFA on obesity at the cellular level was also investigated, using adipocyte hypertrophy as the outcome measure of adipose tissue enlargement. A diet high in n-3 PUFA prevented adipocyte hypertrophy in males, with no effect in females. High n-3 PUFA diet also led to the downregulation of the mRNA expression of acyl CoA:diacylglycerol acyltransferase 2 (DGAT2), fatty acid binding protein-4 (FABP4), peroxisome proliferator-activated receptor protein γ (PPARγ), and leptin in males, which are key proteins involved in adipocyte hypertrophy; however no effect was observed in females. The last study assessed the effects of dose and duration of exposure to dietary n-3 PUFA on DHA accretion in the brain, and the expression of neurotrophins kn...

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Unsaturated Fatty Acids Esterified in 2‐Acyl‐1‐Lysophosphatidylcholine Bound to Albumin Are More Efficiently Taken up by the Young Rat Brain than the Unesterified Form

Cited by 116 publications

References 36 publications

Effects of Dietary Docosahexaenoic Acid Connecting Phospholipids on the Learning Ability and Fatty Acid Composition of the Brain

Effects of Dietary Docosahexaenoic Acid Connecting Phospholipids on the Learning Ability and Fatty Acid Composition of the Brain

Evidence for altered positional specificity of LCAT in vivo

Lipid metabolism and the risk factors of cardiovascular disease: implication of dietary omega-3 polyunsaturated fatty acids

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