Scope
The fatty acid composition of plasma lipids, which is associated with biomarkers and risk of non‐communicable diseases, is regulated by dietary polyunsaturated fatty acids (PUFAs) and variants ...of fatty acid desaturase (FADS). We investigated the interactions between dietary PUFAs and FADS1 rs174550 variant.
Methods and results
Participants (n = 118), homozygous for FADS1 rs174550 variant (TT and CC) followed a high alpha‐linolenic acid (ALA, 5 percent of energy (E‐%)) or a high linoleic acid (LA, 10 E‐%) diet during an 8‐week randomized controlled intervention. Fatty acid composition of plasma lipids and PUFA‐derived lipid mediators were quantified by gas and liquid chromatography mass spectrometry, respectively. The high‐LA diet increased the concentration of plasma LA, but not its lipid mediators. The concentration of plasma arachidonic acid decreased in carriers of CC and remained unchanged in the TT genotype. The high‐ALA diet increased the concentration of plasma ALA and its cytochrome P450‐derived epoxides and dihydroxys, and cyclooxygenase‐derived monohydroxys. Concentrations of plasma eicosapentaenoic acid and its mono‐ and dihydroxys increased only in TT genotype carriers.
Conclusions
These findings suggest the potential for genotype‐based recommendations for PUFA consumption, resulting in modulation of bioactive lipid mediators which can exert beneficial effects in maintaining health.
This study aimed to explore the differences in the plasma fatty acid and lipid mediator concentrations in response to dietary polyunsaturated fatty acids (PUFA) between carriers of the FADS1 rs174550 TT and CC genotypes. Plasma concentrations of long‐chain PUFAs and their derived bioactive lipid mediators changed in a genotype dependent manner in response to linoleic and alpha‐linolenic acid enriched diets.
•Dietary short and long chain n-3 fatty acids modify lipid mediator profiles.•Eating of fatty fish increases concentrations of hydroxy derivatives of EPA and DHA.•Changes in n-3 lipid mediator ...concentrations follow the intake of their precursor PUFA.
n-3 and n-6 polyunsaturated fatty acids (PUFAs) and their lipid mediator metabolites are associated with inflammation. We investigated the effect of dietary intake of plant- and animal-derived n-3 PUFAs and fish protein on the circulatory concentrations of lipid mediators. Seventy-nine subjects with impaired fasting glucose who completed the controlled dietary intervention after randomization to the fatty fish (FF, n=20), lean fish (LF, n=21), Camelina sativa oil (CSO, n=18) or control group (n=20) for 12 weeks were studied. Lipid mediator profiling from fasting plasma samples before and after the intervention was performed by liquid chromatography-mass spectrometry (LC-MS/MS). The FF diet increased concentrations of 18-hydroxyeicosapentaenoic acid (18-HEPE) and 4- and 17-hydroxydocosahexaenoic acid (4-, 17-HDoHE) derived from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), respectively. Concentrations of lipid mediators derived from α-linolenic acid (ALA) increased and arachidonic acid (AA) derived 5-iso prostaglandin F2α-VI decreased in the CSO group. There were no significant changes in lipid mediators in the LF group. The dietary intake of both plant and animal-based n-3 PUFAs increased circulatory concentrations of lipid mediators with potential anti-inflammatory properties.
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Aims/hypothesis The transcription factor nuclear factor-kappa-B (NFκB) is implicated in inflammatory responses, obesity and the metabolic syndrome, while immune cells appear to play a central role in ...mediating insulin resistance and can be used as a model to study inflammation and its relationship with insulin resistance. In peripheral blood mononuclear cells of overweight participants with the metabolic syndrome, we evaluated (1) the effect of diet-induced weight loss on the expression of genes involved in NFκB activation and (2) their association with insulin sensitivity. The genes studied were: TNF receptors TNFRSF1A and TNFRSF1B, and IL1R1, TLR4, TLR2, ICAM1, CCL5 and IKBKB. Methods We analysed data from 34 overweight participants with abnormal glucose metabolism and the metabolic syndrome, who were randomised to a weight-reduction (n = 24) or control group (n = 10) for 33 weeks. The mRNA expression was measured using real-time PCR. Measures of insulin and glucose homeostasis were assessed by IVGTT and OGTT. Results In general, the genes studied were downregulated after weight loss intervention. The changes in TLR4, TLR2, CCL5 and TNFRSF1A mRNA expression were associated with an increase in insulin sensitivity index independently of the change in waist circumference (p < 0.05). The change in IKBKB expression correlated with most of the changes in gene expression in the weight-reduction group. Conclusions/interpretation These results suggest that proteins encoded by CCL5, TLR2 and TLR4, and TNFRSF1A might contribute to insulin-resistant states that characterise obesity and the metabolic syndrome. Trial registration: ClinicalTrials.gov NCT 00621205
Molecular mechanisms linking fish and vegetable oil intakes to their healthy metabolic effects may involve attenuation of inflammation. Our primary aim was to examine in a randomized controlled ...setting whether diets enriched in fatty fish (FF), lean fish (LF) or ALA-rich camelina sativa oil (CSO) differ in their effects on the mRNA expression response of selected inflammation-related genes in peripheral blood mononuclear cells (PBMCs) and subcutaneous adipose tissue (SAT) in subjects with impaired fasting glucose.
Samples from 72 participants randomized to one of the following 12-week intervention groups, FF (n = 19), LF (n = 19), CSO (n = 17) or a control group (n = 17), were available for the PBMC study. For SAT, 39 samples (n = 8, n = 10, n = 9, n = 12, respectively) were available. The mRNA expression was measured at baseline and 12 weeks by TaqMan® Low Density Array.
In PBMCs, LF decreased ICAM1 mRNA expression (P < 0.05), which was different (P = 0.06, Bonferroni correction) from the observed increase in the FF group (P < 0.05). Also, compared to the control group, LF decreased ICAM1 mRNA expression (P < 0.05). Moreover, the change in ICAM1 mRNA expression correlated positively with the intake of FF (P < 0.05) and negatively with the intake of LF (P < 0.05), independently of study group. A diet enriched in CSO, a rich source of alpha-linolenic acid (ALA), decreased PBMC IFNG mRNA expression (P < 0.01). The intake of CSO in the CSO group, but not the increase in plasma ALA proportions, correlated inversely with the IFNG mRNA expression in PBMCs (P = 0.08). In SAT, when compared with the control group, the effect of FF on decreasing IL1RN mRNA expression was significant (P < 0.03).
We propose that CSO intake may partly exert its benefits through immuno-inflammatory molecular regulation in PBMCs, while modulation of ICAM1 expression, an endothelial/vascular-related gene, may be more dependent on the type of fish consumed.
Blood lipid fractions serve as objective biomarkers of dietary fat intake. It is unclear which fatty acid pool most accurately reflects the dietary intakes of different n-3 PUFAs. We aimed to ...investigate the effect of fish and camelina sativa oil (CSO) intakes on fatty acid composition of erythrocyte membranes (EM), plasma phospholipids (PL), cholesteryl esters (CE) and triglycerides (TG). We also aimed to identify the most appropriate blood lipid fraction for assessing n-3 PUFA intake.
Altogether 79 volunteers with impaired glucose metabolism were randomly assigned either to CSO, fatty fish, lean fish or control groups for 12 weeks. Fatty acid compositions of lipid pools were measured by gas chromatography. The proportion of alpha-linolenic acid (ALA) increased in all lipid pools in the CSO group (false discovery rate (FDR) p < 0.001 for all). Similarly, the proportions of EPA and DHA increased in all lipid fractions in the fatty fish group (FDR p < 0.001 for EM, PL and CE; FDR p = 0.005 for TG; FDR p < 0.001 for EM, PL, CE; FDR p < 0.007 for TG, respectively). Changes in the dietary intakes of ALA, EPA and DHA correlated with the changes in their proportions in all lipid pools (r = 0.3–0.5, p < 0.05).
There is no difference in the ability of blood lipid fractions in reflecting the dietary intake of different n-3 PUFAs over a time period of 12 weeks in subjects with high baseline omega-3 index.
This trial was registered in Clinicaltrials.gov (NCT01768429)
•Any blood lipid fraction can be used as biomarker for n-3 PUFA intake.•Intake of fatty fish increases the levels of EPA and DHA in blood lipid fractions.•Intake of camelina sativa oil does not increase levels of DHA in lipid fractions.
The transcription factor nuclear factor-kappa-B (NFκB) is implicated in inflammatory responses, obesity and the metabolic syndrome, while immune cells appear to play a central role in mediating ...insulin resistance and can be used as a model to study inflammation and its relationship with insulin resistance. In peripheral blood mononuclear cells of overweight participants with the metabolic syndrome, we evaluated (1) the effect of diet-induced weight loss on the expression of genes involved in NFκB activation and (2) their association with insulin sensitivity. The genes studied were: TNF receptors TNFRSF1A and TNFRSF1B, and IL1R1, TLR4, TLR2, ICAM1, CCL5 and IKBKB. We analysed data from 34 overweight participants with abnormal glucose metabolism and the metabolic syndrome, who were randomised to a weight-reduction (n=24) or control group (n=10) for 33 weeks. The mRNA expression was measured using real-time PCR. Measures of insulin and glucose homeostasis were assessed by IVGTT and OGTT. In general, the genes studied were downregulated after weight loss intervention. The changes in TLR4, TLR2, CCL5 and TNFRSF1A mRNA expression were associated with an increase in insulin sensitivity index independently of the change in waist circumference (p<0.05). The change in IKBKB expression correlated with most of the changes in gene expression in the weight-reduction group. These results suggest that proteins encoded by CCL5, TLR2 and TLR4, and TNFRSF1A might contribute to insulin-resistant states that characterise obesity and the metabolic syndrome. Trial registration: ClinicalTrials.gov NCT 00621205 PUBLICATION ABSTRACT
The transcription factor nuclear factor-kappa-B (NFkappaB) is implicated in inflammatory responses, obesity and the metabolic syndrome, while immune cells appear to play a central role in mediating ...insulin resistance and can be used as a model to study inflammation and its relationship with insulin resistance. In peripheral blood mononuclear cells of overweight participants with the metabolic syndrome, we evaluated (1) the effect of diet-induced weight loss on the expression of genes involved in NFkappaB activation and (2) their association with insulin sensitivity. The genes studied were: TNF receptors TNFRSF1A and TNFRSF1B, and IL1R1, TLR4, TLR2, ICAM1, CCL5 and IKBKB.
We analysed data from 34 overweight participants with abnormal glucose metabolism and the metabolic syndrome, who were randomised to a weight-reduction (n = 24) or control group (n = 10) for 33 weeks. The mRNA expression was measured using real-time PCR. Measures of insulin and glucose homeostasis were assessed by IVGTT and OGTT.
In general, the genes studied were downregulated after weight loss intervention. The changes in TLR4, TLR2, CCL5 and TNFRSF1A mRNA expression were associated with an increase in insulin sensitivity index independently of the change in waist circumference (p < 0.05). The change in IKBKB expression correlated with most of the changes in gene expression in the weight-reduction group.
These results suggest that proteins encoded by CCL5, TLR2 and TLR4, and TNFRSF1A might contribute to insulin-resistant states that characterise obesity and the metabolic syndrome.
ClinicalTrials.gov NCT 00621205.
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