Phospholipid Long-chain Polyunsaturated Fatty Acids Research Articles

Ethnicity, plasma phospholipid fatty acid composition and inflammatory/endothelial activation biomarkers in the Multi-Ethnic Study of Atherosclerosis (MESA)

It has been recognized that certain long-chain polyunsaturated fatty acids (LC-PUFAs) are involved in inflammation and its resolution. It has also been shown that ethnicity may be a factor in affecting systemic inflammation, and limited evidence suggests it may influence plasma LC-PUFA composition. Given the links among these three factors, we aim to determine ethnicity-based differences in plasma LC-PUFA composition among White, Black, Hispanic and Chinese participants, and whether such differences contribute to variations in markers of inflammation and endothelial activation in a sub-cohort of the Multi-Ethnic Study of Atherosclerosis (MESA). Plasma phospholipid LC-PUFAs levels (%) were determined in 2848 MESA participants using gas chromatography-flame ionization detection. Enzyme immunoassays determined inflammatory markers levels for high-sensitivity C-reactive protein (n=2848), interleukin-6 (n=2796), soluble tumor necrosis factor-α receptor type 1 (n=998), and endothelial activation markers soluble intercellular adhesion molecule-1 (n=1192) and soluble E-selectin (n=998). The modifying influence of ethnicity was tested by linear regression analysis. Chinese adults were found to have the highest mean levels of plasma eicosapentaenoic acid (EPA, 1.24%) and docosahexaenoic acid (DHA, 4.95%), and the lowest mean levels of γ-linolenic (0.10%), dihomo-γ-linolenic (DGLA, 2.96%) and arachidonic (10.72%) acids compared with the other ethnicities (all P ≤ 0.01). In contrast, Hispanics had the lowest mean levels of plasma EPA (0.70%) and DHA (3.49%), and the highest levels of DGLA (3.59%; all P ≤ 0.01). Significant differences in EPA and DHA among ethnicities were attenuated following adjustment for dietary non-fried fish and fish oil supplementation. Ethnicity did not modify the associations of LC-PUFAs with markers of inflammation or endothelial activation (all P (interaction)>0.05). The absence of a modifying effect of ethnicity indicates that the putative benefits of LC-PUFAs with respect to inflammation are pan-ethnic. Future longitudinal studies may elucidate the origin(s) of ethnicity-based differences in LC-PUFA composition and whether certain patterns, that is, high plasma levels of DGLA and low levels of EPA/DHA, contribute to inflammation-associated health outcomes.

Omega-3 long chain fatty acid synthesis is regulated more by substrate levels than gene expression

The conversion of linoleic acid (LA) and alpha-linolenic acid (ALA) to long chain polyunsaturated fatty acids (LCPUFA) is known to involve desaturation and elongation steps. Although there is evidence that genes for these steps can be regulated by extremes of dietary PUFA, the degree to which there is meaningful regulation of LCPUFA levels in tissues by diet as a result of changes in expression of desaturase and elongase genes is unclear. In this study, we tested the effect of increasing ALA levels in diets of rats from 0.2% to 2.9% energy (en) against a constant LA level (1%en) on plasma and liver phospholipid LCPUFA content together with the expression of hepatic genes involved in PUFA metabolism, the desaturases FADS1 and FADS2, the elongases ELOV2 and ELOV5, and the transcription factors sterol regulatory element-binding protein-1c (SREBP-1c) and peroxisome proliferator-activated receptor alpha (PPARα). The levels of plasma and liver eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA) increased in proportion to dietary ALA whereas docosahexaenoic acid (DHA) increased only up to 1%en ALA. A low PUFA (0.4%en) reference diet stimulated the expression of delta 6 desaturase (FADS2) and elongase 2 (ELOVL2) when compared to higher PUFA diets. There was, however, no difference in the expression of any of the genes in rats, which were fed diets containing between 0.2%en and 2.9%en ALA and mRNA expression was unrelated to tissue/plasma LCPUFA content. These data suggest that the endogenous synthesis of n−3 LCPUFA from the precursor ALA is regulated independently of changes in the expression of the synthetic enzymes or regulatory transcription factor, and provides evidence that n−3 LCPUFA synthesis is regulated more by substrate competition for existing enzymes than by an increase in their mRNA expression.

Fish consumption, not fatty acid status, is related to quality of life in a healthy population

Depressive symptoms in the community have a considerable impact on quality of life. Although long-chain polyunsaturated fatty acids (LCPUFA) have frequently been implicated in depressed mood, their relationship with quality of life has scarcely been investigated. This study examined the cross-sectional associations between fish consumption and plasma phospholipid LCPUFA status on the one hand, and quality of life, as measured by the Short Form 36 questionnaire, on the other in a population-based sample. The mental health component of quality of life was not associated with LCPUFA status or fish consumption. Fish consumption showed a positive association with physical well-being, which remained significant after correction for LCPUFA status, suggesting that the relationship between fish consumption and physical well-being is independent of the LCPUFA content of fish. These findings indicate that fish consumption may serve as a proxy for a healthy lifestyle or a favorable nutritional status, which is reflected in better quality of life.

The Relationship of Insulin Resistance With SNP 276G>T at Adiponectin Gene and Plasma Long-Chain Polyunsaturated Fatty Acids in Obese Children

This study examined the association of insulin resistance with single-nucleotide polymorphism (SNP) 276G>T at adiponectin gene and the plasma long-chain polyunsaturated fatty acids (LCPUFAs) profile in obese children. One hundred thirty-one normolipidaemic obese children aged 8-13 y (53 girls and 68 boys) entered the study. The prevalence of T allele carriers at SNP276 was 48.8%. Mean [SD] values of fasting insulin and homeostasis model assessment-insulin resistance (HOMA-IR) index in noncarriers versus carriers of T allele were 12.4 [6.4] versus 20.6 [6.3] muU/mL (p = 0.039) and 2.6 [1.4] versus 4.5 [1.7] (p = 0.032). Mean [SD] values of plasma C18:3n - 3, C20:5n - 3/C20:4n - 6, and n - 6/n - 3 LCPUFA in phospholipids in noncarriers versus carriers of T allele were 0.10 [0.04] versus 0.08 [0.03] % (p = 0.013), 0.04 [0.01] versus 0.03 [0.01] % (p = 0.045), and 4.4 [0.7] versus 4.9 [0.9] % (p = 0.005), respectively. Insulin resistance was independently associated with SNP 276G>T (p = 0.002) and n - 6/n - 3 LCPUFA (p = 0.042) in plasma phospholipids, and interaction was found between SNP 276G>T and n - 6/n - 3 LCPUFA (p = 0.046). These findings suggest that obese children carriers of the SNP 276G>T may be at increased risk of metabolic complications compared with noncarriers, possibly due in part to a different plasma phospholipids profile.

Plasma phospholipid fatty acid status and depressive symptoms: Association only present in the clinical range

Background Long-chain polyunsaturated fatty acids (LCPUFA) have been implicated in depression, but their role in mood variability in the general population is still unclear. We investigated the associations between LCPUFA status or fish consumption on the one hand and depressive symptoms and chronicity of depressed mood on the other in a community-based sample. Methods Plasma phospholipid LCPUFA profiles of 241 participants of the Maastricht Aging Study (MAAS) were determined. Depressive symptoms were measured using the CES-D and SCL-90 questionnaires. Using linear regression analyses, associations between the actual level and longitudinal (12-year) variability in depressive symptoms on the one hand and LCPUFA concentrations or fish consumption on the other were examined. Results No linear associations were found in the total sample between depressive symptoms and LCPUFA concentrations or fish consumption. Chronicity of depressed mood was also not related to LCPUFA status or fish consumption. Post-hoc analyses, however, showed a negative correlation between docosahexaenoic acid (DHA, 22:6 n-3) concentration and depressed mood in persons with CES-D scores above the clinical threshold. Regression analysis suggested a non-linear association between depressive symptoms and DHA concentration in the total sample. Limitations The cross-sectional nature of the present study did not allow for inferences about causality. Conclusions This study offers a first indication that a suboptimal LCPUFA status might accompany depressive symptoms primarily within the clinical spectrum.

The fatty acid composition of skeletal muscle membrane phospholipid: Its relationship with the type of feeding and plasma glucose levels in young children

Long-chain polyunsaturated fatty acids (LCPUFAs), including docosahexaenoic acid ([DHA] 22:6 n-3), are important components of cell membranes. Low levels of DHA and other LCPUFAs in skeletal muscle membrane phospholipid are associated with insulin resistance and obesity in adults. These findings may be influenced by both dietary and genetic factors. This study aimed to investigate the interrelationships between the type of infant feeding, skeletal muscle phospholipid fatty acid (FA) composition, and glucoregulation in young children. Skeletal muscle biopsies and fasting blood samples were obtained from 56 normally nourished young children (35 males and 21 females) aged less than 2 years (mean ± SE, 0.76 ± 0.06) undergoing elective surgery. The dietary history was taken, and muscle phospholipid FA composition was analyzed. Subgroups of totally breast-fed and age-matched formula-fed infants were compared. Breast-fed infants (n = 13; age, 0.54 ± 0.06 years) had a significantly higher percentage of DHA (3.63% ± 0.22% v 1.84% ± 0.11%, P < .0001) and total percentage of LCPUFAs (30.24 ± 0.87% v 25.17% ± 0.86, P < .0001) in muscle phospholipids compared with the formula-fed ground (n = 12; age, 0.59 ± 0.08 years). The totally breast-fed group had lower plasma glucose levels than the formula-fed grou (4.7 ± 0.2 v 5.4 ± 0.2 mmol/L, P < .02). Consistent with these findings, further analysis of a group of 39 children who had either never or not recently been breast-fed showed significant inverse correlations between fasting plasma glucose and the percentage of both DHA ( r = −.47, P < .003) and total LCPUFAs ( r = −.38, P < .05). The results of this study show that (1) breast-feeding increases LCPUFA levels in skeletal muscle membrane and (2) early development of relatively higher levels of LCPUFAs in the phospholipid of skeletal muscle, influenced both by type of feeding and by genetic predisposition, is associated with lower fasting plasma glucose. Early changes in skeletal muscle membrane phospholipid FA saturation may play a role in the subsequent development of diseases associated with insulin resistance.

Intercommunication between brain capillary endothelial cells and astrocytes: Upregulation of the LDL receptor at the BBB

Several physiological processes, such as visual and cognitive development in early life, are dependent on the availability of long-chain polyunsaturated fatty acids (LC-PUFAs). Furthermore, the concentration of LC-PUFAs in phospholipids has been associated with numerous complex diseases like cardiovascular disease, atopic disease and metabolic syndrome. The level and composition of LC-PUFAs in the human body is mainly dependent on their dietary intake or on the intake of fatty acid precursors, which are endogenously elongated and desaturated to physiologically active LC-PUFAs. The delta-5 and delta-6 desaturase are the most important enzymes in this reaction cascade. In the last few years, several studies have reported an association between single nucleotide polymorphisms (SNPs) in the two desaturase encoding genes (FADS1 and FADS2) and the concentration of omega-6 and omega-3 fatty acids. This shows that beside nutrition, genetic factors play an important role in the regulation of LC-PUFAs as well. This review focuses on current knowledge of the impact of FADS genotypes on LC-PUFA and lipid metabolism and discusses their influence on infant intellectual development, neurological conditions, metabolic disease as well as cardiovascular disease.

Effects of inhibitors of protein and RNA synthesis on aldosterone-stimulated changes in phospholipid fatty acid metabolism in the toad urinary bladder

The effects of an inhibitor of RNA synthesis, cordycepin, and an inhibitor of protein synthesis, cycloheximide, on aldosterone-induced changes in lipid metabolism and phospholipid fatty acid composition have been studied in the toad urinary bladder. At the concentrations employed, the inhibitors abolish the hormone-induced increases in total lipid synthesis, phospholipid fatty acid specific activities, and weight percentage of phospholipid long-chain polyunsaturated fatty acids as well as blocking the aldosterone-mediated increase in sodium transport.

Effects of an acetyl-coenzyme A carboxylase inhibitor and a sodium-sparing diuretic on aldosterone-stimulated sodium transport, lipid synthesis, and phospholipid fatty acid composition in the toad urinary bladder

A correlation study of the effects of two agents, 2-methyl-2-[p-(1,2,3,4-tetrahydro-1-naphthyl)phenoxy]propionic acid (TPIA) and amiloride, on aldosterone-induced alterations in Na+ transport, lipid synthesis, and phospholipid fatty acid composition has been carried out in the toad urinary bladder. TPIA, an inhibitor of acetyl-CoA carboxylase, inhibits aldosterone-stimulated Na+ transport as well as hormone-induced lipid synthesis and the increase in weight percentage of phospholipid long-chain polyunsaturated fatty acids. Amiloride, a diuretic which blocks sodium entry into the transporting epithelium, does not alter aldosterone's effects on lipid and fatty acid metabolism but prevents the hormone-induced increase in Na+ transport. These results support the conclusion that aldosterone increases Na+ transport in the toad urinary bladder by altering membrane fatty acid metabolism and that the lipid biosynthetic events following aldosterone treatment are a primary response to the hormone and not secondary to increased Na+ transport.