Docosahexaenoic Acid and Eicosapentaenoic Acid Did not Alter trans-10,cis-12 Conjugated Linoleic Acid Incorporation into Mice Brain and Eye Lipids.

trans 10,cis 12-CLA has been reported to alter fatty acid composition in several non-neurological tissues, but its effects are less known in neurological tissues. Therefore, the purpose of this study was to determine if CLA supplementation would alter brain and eye fatty acid composition and if those changes could be prevented by concomitant supplementation with docosahexaenoic acid (DHA; 22:6n3) or eicosapentaenoic acid (EPA; 20:5n3). Eight-week-old, pathogen-free C57BL/6N female mice (n = 6/group) were fed either the control diet or diets containing 0.5% (w/w) t10,c12-CLA in the presence or absence of either 1.5% DHA or 1.5% EPA for 8 weeks. CLA concentration was significantly (P < 0.05) greater in the eye but not in the brain lipids of the CLA group when compared with the control group. The sums of saturated, monounsaturated, polyunsaturated fatty acids, and n3:n6 ratio did not differ between these two groups for both tissues. The n3:n6 ratio and concentrations of 20:5n3 and 22:5n3 were significantly greater, and those of 20:4n6, 22:4n6, and 22:5n6 were lesser in the CLA + DHA and CLA + EPA groups than in the control and CLA groups for either tissue. DHA concentration was higher in the CLA + DHA group only but not in the CLA + EPA group when compared with the CLA group for both tissues. The dietary fatty acids generally induced similar changes in brain and eye fatty acid concentration and at the concentrations used both DHA and EPA fed individually with CLA were more potent than CLA alone in altering the tissue fatty acid concentration.

Modulation of blood cell gene expression by DHA supplementation in hypertriglyceridemic men.

Our previous study with docosahexaenoic acid (DHA) supplementation to hypertriglyceridemic men showed that DHA reduced several risk factors for cardiovascular disease, including the plasma concentration of inflammatory markers. To determine the effect of DHA supplementation on the global gene expression pattern, we performed Affymetrix GeneChip microarray analysis of blood cells [treated with lipopolysaccharide (LPS) or vehicle] drawn before and after the supplementation of DHA from the hypertriglyceridemic men who participated in that study. Genes that were significantly differentially regulated by the LPS treatment and DHA supplementation were identified. Differential regulation of 18 genes was then verified by quantitative real-time polymerase chain reaction (qRT-PCR). Both microarray and qRT-PCR data showed that DHA supplementation significantly suppressed the expression of low-density lipoprotein (LDL) receptor and cathepsin L1, both of which were also up-regulated by LPS. DHA supplementation also suppressed oxidized LDL (lectin-like) receptor 1 (OLR1). However, LPS did not induce OLR1 mRNA expression. Enrichment with Gene Ontology categories demonstrated that the genes related to transcription factor activity, immunity, host defense and inflammatory responses were inversely regulated by LPS and DHA. These results provide supporting evidence for the anti-inflammatory effects of DHA supplementation, and reveal previously unrecognized genes that are regulated by DHA and are associated with risk factors of cardiovascular diseases.

Flaxseed oil prevents trans-10, cis-12-conjugated linoleic acid-induced insulin resistance in mice.

Insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD) are found in 35 and 30 % of US adults, respectively. Trans-10, cis-12-conjugated linoleic acid (CLA) has been found to cause both these disorders in several animal models. We hypothesised that IR and NAFLD caused by CLA result from n-3 fatty acid deficiency. Pathogen-free C57BL/6N female mice (aged 8 weeks; n 10) were fed either a control diet or diets containing trans-10, cis-12-CLA (0.5 %) or CLA+flaxseed oil (FSO) (0.5 %+0.5 %) for 8 weeks. Weights of livers, concentration of circulating insulin, values of homeostatic model 1 (HOMA1) for IR and HOMA1 for beta cell function were higher by 160, 636, 985 and 968 % in the CLA group compared with those in the control group. FSO decreased fasting glucose by 20 % and liver weights by 37 % compared with those in the CLA group; it maintained circulating insulin, HOMA1-IR and HOMA1 for beta cell function at levels found in the control group. CLA supplementation decreased n-6 and n-3 wt% concentrations of liver lipids by 57 and 73 % and increased the n-6:n-3 ratio by 58 % compared with corresponding values in the control group. FSO increased n-6 and n-3 PUFA in liver lipids by 33 and 342 % and decreased the n-6:n-3 ratio by 70 % compared with corresponding values in the CLA group. The present results suggest that some adverse effects of CLA may be due to n-3 PUFA deficiency and that these can be corrected by a concomitant increase in the intake of alpha-linolenic acid, 18 : 3n-3.

Docosahexaenoic acid supplementation decreases remnant-like particle-cholesterol and increases the (n-3) index in hypertriglyceridemic men.

Plasma remnant-like particle-cholesterol (RLP-C) and the RBC (n-3) index are novel risk factors for cardiovascular disease. Effects of docosahexaenoic acid (DHA) supplementation on these risk factors in hypertriglyceridemic men have not been studied. We determined effects of DHA supplementation on concentrations of plasma RLP-C, the RBC (n-3) index, and associations between concentrations of plasma RLP-C with those of plasma lipids and fatty acids. Hypertriglyceridemic men aged 39-66 y, participated in a randomized, placebo-controlled, parallel study. They received no supplements for 8 d and then received either 7.5 g/d DHA oil (3 g DHA/d) or olive oil (placebo) for the last 90 d. Fasting blood samples were collected on study d -7, 0 (baseline), 45 (mid-intervention), 84, and 91 (end-intervention). DHA supplementation for 45 d decreased (P < 0.05) fasting RLP-C (36%) and increased plasma eicosapentaenoic acid (EPA):arachidonic acid (AA) (100%) and the RBC (n-3) index (109%). Continued supplementation with DHA between d 45 and 91 further increased the RBC (n-3) index (162%) and plasma EPA:AA (137%) compared with baseline values. RLP-C concentration was positively associated (P < 0.01) with the plasma concentrations of triacylglycerols (Kendall's correlation coefficient or r = 0.46), triacylglycerol:HDL cholesterol (HDL-C) (r = 0.44), total cholesterol:HDL-C (r = 0.26), Apo B (r = 0.22), C III (r = 0.41), and E (r = 0.17), and 18:1(n-9) (r = 0.32); it was negatively associated (P < 0.05) with plasma concentrations of DHA (r = -0.32), EPA (r = -0.25), HDL-C (r = -0.21), LDL cholesterol:Apo B (r = -0.30), and HDL-C:Apo A (r = -0.25). Supplementation with placebo oil did not alter any of the response variables tested. Decreased atherogenic RLP-C and increased cardio-protective (n-3) index may improve cardio-vascular health.

Docosahexaenoic acid supplementation improves fasting and postprandial lipid profiles in hypertriglyceridemic men.

BACKGROUND: The effects of docosahexaenoic acid (DHA) on the mean size and concentrations of VLDL, LDL, and HDL subclasses have not been previously studied. OBJECTIVE: We determined the effects of DHA supplementation on the concentrations of apoproteins; large, medium, and small VLDL, LDL, and HDL particles; and the mean diameters of these particles in fasting and postprandial plasma. DESIGN: Hypertriglyceridemic men aged 39-66 y (n = 34) participated in a double-blind, randomized, placebo-controlled parallel study. They received no supplements for the first 8 d and received either 7.5 g DHA oil/d (3 g DHA/d) or olive oil (placebo) for the last 90 d. Lipoprotein particle diameters and concentrations were measured by nuclear magnetic resonance spectroscopy. RESULTS: DHA supplementation for 45 d significantly (P < 0.05) decreased concentrations of fasting triacylglycerol (24%), large VLDL (92%), and intermediate-density lipoproteins (53%) and the mean diameter of VLDL particles (11.1 nm). It elevated concentrations of LDL cholesterol (12.6%), small VLDL particles (133%), and large LDL particles (120%) and the mean diameter of LDL particles (0.6 nm) in fasting plasma. Similar changes were observed for area under the curve for postprandial samples (0-6 h); however, the number of small dense LDL particles decreased significantly (21%), and the change in LDL cholesterol was not significant. Continued supplementation with DHA beyond 45 d caused no further changes; placebo treatment altered none of the responses tested. CONCLUSION: DHA supplementation may improve cardiovascular health by lowering concentrations of triacylglycerols and small, dense LDL particles.

Docosahexaenoic Acid (DHA) But Not Eicosapentaenoic Acid (EPA) Prevents Trans-10, Cis-12 Conjugated Linoleic Acid (CLA)-Induced Insulin Resistance in Mice.

BACKGROUND: The objective of this study was to investigate if eicosapentaenoic acid (20:5n-3, EPA) or docosahexaenoic acid (22:6n-3, DHA) or both would prevent conjugated linoleic acid (CLA)-induced insulin resistance and fatty liver. METHODS: Eight-week-old, pathogen-free C57BL/6N female mice (10 per group) were fed either a control diet or diets containing t10, c12-CLA (0.5 wt %), CLA + DHA (0.5% + 1.5 wt %), or CLA + EPA (0.5% + 1.5 wt %) for 8 weeks prior to sacrifice and tissue collection. RESULTS: CLA supplementation caused an 8.9-fold increase in circulating insulin, a 2.6-fold increase in liver weight, and a 6.2-fold increase in the weight of total lipids in the liver as compared with the corresponding values in the control group. DHA prevented the CLA-induced insulin resistance, while EPA was ineffective. Both EPA and DHA prevented CLA-induced fatty liver and reduced weights of total liver lipids to the levels of the control group. CLA also reduced the plasma leptin and adiponectin concentrations to approximately 15% of those in the control group. Both EPA and DHA partially restored the CLA-induced decrease in leptin, but only DHA partially restored the plasma adiponectin. CONCLUSIONS: Our results suggest that DHA but not EPA in fish oils may reduce insulin resistance which may be mediated through an increase in circulating adiponectin. These findings may have clinical implications in the dietary management of patients at risk of insulin resistance and diabetes.

Fatty acid composition of liver, adipose tissue, spleen, and heart of mice fed diets containing t10, c12-, and c9, t11-conjugated linoleic acid.

Conjugated linoleic acid (CLA) isomers have unique effects on tissue lipids. Here we investigated the influence of individual CLA isomers on the lipid weight and fatty acid composition of lipid metabolizing (i.e. liver and retroperitoneal adipose) and lipid sensitive (i.e. spleen and heart) tissues. Female mice (8 week old; n=6/group) were fed either a control or one of the two CLA isomer supplemented (0.5%) diets for 8 weeks. The cis-9, trans-11-CLA diet reduced the 18:1n-9 wt% by 20-50% in liver, adipose tissue, and spleen, reduced the spleen n-3 polyunsaturated fatty acid (PUFA) by 90%, and increased the n-6 PUFA wt% by 20-50% in all tissues except heart. The trans-10, cis-12-CLA reduced both the n-6 and n-3 PUFA wt% in liver (>50%), reduced the heart n-3 PUFA wt% by 25%, and increased the wt% of spleen n-3 PUFA by 700%. The functional consequences of such changes in tissue fatty acid composition need to be investigated.