Consumption Of Long-chain Research Articles

Effect of n‐3 fatty acids and their derivatives on the expression of inflammatory genes (1034.15)

Background: Uncontrolled inflammation participates in the development of chronic inflammatory diseases. Beneficial effects of the consumption of long chain n‐3 polyunsaturated fatty acids (PUFAs), mostly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on inflammation have been reported. Lipid mediators produced from EPA and DHA (resolvins) play a central role in the resolution of inflammation. Objective: To study the effects of EPA, DHA, resolvin D1 (RvD1) and resolvin D2 (RvD2) on the expression of inflammatory genes in cultured THP1 macrophages. Methods: Cells were incubated for 6h and 24h in the presence of n‐3 PUFAs (EPA, DHA; 100, 50, 25, 10 μM and resolvins (RvD1, RvD2; 1μM, 100, 50, 25, 10 nM). Total RNA was isolated and TNF‐alpha, IL‐6 and IL‐10 mRNA levels were analyzed by real‐time PCR. Results: In THP1 cells, EPA, DHA, RvD1 and RvD2 down‐regulated IL‐6 and TNF‐alpha gene expression, and up‐regulated IL‐10 expression in a time‐dependent manner with higher extent observed after 24h. TNF‐alpha, IL‐6 and IL‐10 gene expression demonstrated a dose‐dependent response following treatment with EPA and DHA (10, 25 and 50 μM). No association was found between gene expression and resolvins concentrations in dose‐response experiments. Conclusion: We demonstrate a time‐ and dose‐dependent regulation of TNF‐alpha, IL‐6 and IL‐10 gene expression levels in macrophages under EPA and DHA treatment.Grant Funding Source: NSERC

Long chain polyunsaturated fatty acids alter oxytocin signaling and receptor density in cultured pregnant human myometrial smooth muscle cells.

Epidemiological studies and interventional clinical trials indicate that consumption of long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) such as docosahexaenoic acid (DHA) lengthen gestational duration. Although the mechanisms are not well understood, prostaglandins (PG) of the 2-series are known to play a role in the initiation and progress of labor. In animal studies, modest DHA provision has been shown to reduce placental and uterine PGE2 and PGF2α, matrix metalloproteinase (MMP)-2 and MMP-9 expression, and placental collagenase activity. However, modulation of PG biosynthesis may not account for all the effects of LC n-3 PUFAs in labor. We investigated one potential PG-independent mechanism of LC PUFA action using cultured pregnant human myometrial smooth muscle cells. Our goal was to characterize the effect of LC PUFA treatment on oxytocin signaling, a potent uterotonic hormone involved in labor. The addition of 10 µM–100 µM DHA or arachidonic acid (AA) to the culture media for 48 h resulted in dose dependent enrichment of these fatty acids in membrane lipid. DHA and AA significantly inhibited phosphatidylinositol turnover and [Ca2+]i mobilization with oxytocin stimulation compared to bovine serum albumin control and equimolar oleic acid. DHA and AA significantly reduced oxytocin receptor membrane concentration without altering binding affinity or rate of receptor internalization. These findings demonstrate a role for LC n-3 PUFAs in regulation of oxytocin signaling and provide new insight into additional mechanisms pertaining to reports of dietary fish and fish oil consumption prolonging gestation.

Associations between toenail arsenic concentration and dietary factors in a New Hampshire population.

BackgroundDietary factors such as folate, vitamin B12, protein, and methionine are important for the excretion of arsenic via one-carbon metabolism in undernourished populations exposed to high levels of arsenic via drinking water. However, the effects of dietary factors on toenail arsenic concentrations in well-nourished populations exposed to relatively low levels of water arsenic are unknown.MethodsAs part of a population-based case–control study of skin and bladder cancer from the USA, we evaluated relationships between consumption of dietary factors and arsenic concentrations in toenail clippings. Consumption of each dietary factor was determined from a validated food frequency questionnaire. We used general linear models to examine the associations between toenail arsenic and each dietary factor, taking into account potentially confounding effects.ResultsAs expected, we found an inverse association between ln-transformed toenail arsenic and consumption of vitamin B12 (excluding supplements) and animal protein. Unexpectedly, there were also inverse associations with numerous dietary lipids (e.g., total fat, total animal fat, total vegetable fat, total monounsaturated fat, total polyunsaturated fat, and total saturated fat). Finally, increased toenail arsenic concentrations were associated with increased consumption of long chain n-3 fatty acids.ConclusionIn a relatively well-nourished population exposed to relatively low levels of arsenic via water, consumption of certain dietary lipids may decrease toenail arsenic concentration, while long chain n-3 fatty acids may increase toenail arsenic concentration, possibly due to their association with arsenolipids in fish tissue.

Long chain n − 3 PUFA-rich meal reduced postprandial measures of arterial stiffness

The consumption of long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) is known to be cardio-protective. Data on the influence of LC n-3 PUFA on arterial stiffness in the postprandial state is limited. The aim of this study was to investigate the acute effects of a LC n-3 PUFA-rich meal on measures of arterial stiffness. Twenty-five healthy subjects (12 men, 13 women) received a control and a LC n-3 PUFA-rich meal on two occasions in a random order. Arterial stiffness was measured at baseline, 30, 60, 90, 120, 180 and 240 min after meal consumption by pulse wave analysis and digital volume pulse to derive an augmentation index and a stiffness index respectively. Blood samples were taken for measurement of lipids, glucose and insulin. Consumption of the LC n-3 PUFA-rich meal had an attenuating effect on augmentation index (P=0.02) and stiffness index (P=0.03) compared with the control meal. A significant treatment effect (P=0.036) was seen for plasma non-esterified fatty acids concentrations. These data indicate that acute LC n-3 PUFA-rich meal consumption can improve postprandial arterial stiffness. This has important implications for the beneficial properties of LC n-3 PUFA and cardiovascular risk reduction.

Polyunsaturated fatty acids and inflammation

The n-6 polyunsaturated fatty acid arachidonic acid gives rise to the eicosanoid family of mediators (prostaglandins, thromboxanes, leukotrienes and related metabolites). These have inflammatory actions in their own right and also regulate the production of other mediators including inflammatory cytokines. Consumption of long chain n-3 polyunsaturated fatty acids decreases the amount of arachidonic acid in cell membranes and so available for eicosanoid production. Thus, n-3 polyunsaturated fatty acids decrease production of arachidonic acid-derived eicosanoids. These fatty acids also decrease the production of the classic inflammatory cytokines tumour necrosis factor, interleukin-1, and interleukin-6 and the expression of adhesion molecules involved in inflammatory interactions between leukocytes and endothelial cells. These latter effects may occur by eicosanoid-independent mechanisms including modulation of the activation of transcription factors involved in inflammatory processes. The anti-inflammatory actions of long chain n-3 fatty acid-induced effects may be of therapeutic use in conditions with an acute or chronic inflammatory component.