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Background: Dietary intake of polyunsaturated fatty acids (PUFAs), e.g., linoleic acid and n-3 (ω-3) long-chain PUFAs, has been shown in adults to affect plasma cholesterol and triglycerides (TGs), respectively. Little is known about the effects of PUFAs on plasma lipids in early life.Objective: The aim of this study was to explore the associations between plasma concentrations of total, LDL, and HDL cholesterol and TGs in infants and 2 single nucleotide polymorphisms (SNPs) in the fatty acid desaturase genes (FADS) oppositely associated with docosahexaenoic acid (rs1535 and rs174448) and potential effect modification by a functional peroxisome proliferator-activated receptor-γ2 gene variant (PPARG2 Pro12Ala).Methods: In 9-mo-old infants (n = 561) from 3 Danish cohorts, we analyzed associations between plasma lipids, erythrocyte PUFAs, and FADS SNPs, and interactions with PPARG2 Pro12Ala genotype, by multiple linear regression. We also examined potential effect modification by breastfeeding, as 46% of the infants were still being breastfed.Results: Minor allele carriage of rs174448 was associated with lower total cholesterol (difference: -0.22 mmol/L; 95% CI: -0.37, -0.06 mmol/L; P = 0.006) and LDL cholesterol (difference: -0.15 mmol/L; 95% CI: -0.29, -0.01 mmol/L; P = 0.035), but no associations were observed with TGs or for rs1535. Minor allele carriage of both FADS SNPs was associated with 1 SD lower HDL cholesterol, but only in currently breastfed infants (rs174448 × breastfeeding, P = 0.080; rs1535 × breastfeeding, P = 0.030) and PPARG2 minor allele carriers (rs174448 × PPARG2, P = 0.001; rs1535 × PPARG2, P = 0.004). Erythrocyte arachidonic acid and eicosapentaenoic acid were inversely associated with LDL cholesterol [estimated effect (β): -0.3 mmol/L; 95% CI: -0.06, -0.00 mmol/L per percentage of fatty acids (FA%); P = 0.035] and TGs (β: -0.23 mmol/L; 95% CI: -0.41, -0.05 mmol/L per FA%; P = 0.015), respectively.Conclusions: The observed associations with FADS variants indicate that PUFAs are involved in plasma lipid regulation in 9-mo-old infants. Observed FADS SNP differences and interactions with breastfeeding and PPARG2 warrant additional studies to explore the effects of individual FADS SNPs on PUFA status and potential genetic modification of dietary PUFA effects. [ABSTRACT FROM AUTHOR]

Background: Eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) recommendations are frequently stated at 500 mg/d; however, adherence to these recommendations would result in a large global commercial EPA/DHA production deficit. Previously, our laboratory demonstrated that acute DHA intake in rats can increase the capacity for synthesis-secretion of n-3 (ω-3) polyunsaturated fatty acids (PUFAs).Objective: We aimed to investigate the utility of a dietary DHA cycling strategy that employs 2 wk of repeated DHA feeding for a total of 3 cycles over 12 wk.Methods: Male Long-Evans rats were fed a 10% fat diet by weight comprised of either 1) a 2-wk, 2% α-linolenic acid (ALA, DHA-ALA group 18:3n-3) diet followed by a 2-wk, 2% DHA + 2% ALA diet over 3 consecutive 4-wk periods ("DHA cycling," DHA-ALA group); 2) a 2% DHA + 2% ALA diet (DHA group) for 12 wk; or 3) a 2% ALA-only diet (ALA group) for 12 wk. At 15 wk old, blood and tissue fatty acid concentrations and liver mRNA expression and 13C-DHA natural abundances were determined.Results: DHA concentrations in plasma, erythrocytes, and whole blood between the DHA-ALA group and the DHA groups were not different (P ≥ 0.05), but were 72-110% higher (P < 0.05) than in the ALA group. Similarly, DHA concentrations in liver, heart, adipose, and brain were not different (P ≥ 0.05) between the DHA-fed groups, but were at least 62%, 72%, 320%, and 68% higher (P < 0.05) than in the ALA group in liver, heart, adipose, and skeletal muscle, respectively. Compound-specific isotope analysis indicated that 310% more liver DHA in the DHA-ALA group compared with the DHA group is derived from dietary ALA, and this was accompanied by a 123% and 93% higher expression of elongation of very long-chain (Elovl)2 and Elovl5, respectively, in the DHA-ALA group compared with the ALA group.Conclusions: DHA cycling requires half the dietary DHA while achieving equal blood and tissue DHA concentrations in rats. Implementation of such dietary strategies in humans could reduce the gap between global dietary n-3 PUFA recommendations and commercial production. [ABSTRACT FROM AUTHOR]

We studied the incorporation of the trans-11 vaccenic-1-(13)C acid ((13)C-VA) into milk and endogenous synthesis of cis-9, trans-11 conjugated linoleic acid (CLA) in lactating women. Subjects (n = 4) were 247 +/- 30 d postpartum, weighed 70.8 +/- 3.7 kg, breast-fed at least 6 times/d and consumed self-selected diets. After an overnight fast, they consumed the (13)C-VA (2.5 mg/kg body wt). Milk samples were obtained by complete breast expression at 0, 2, 4, 8, 12, 18, 24, and 48 h post-(13)C-VA ingestion. Lipid was extracted using chloroform:methanol. Fatty acids were methylated and converted to dimethyl disulfide and Diels-Alder derivatives before analysis by gas chromatography mass spectrometry. The mean (13)C-enrichment of milk VA was 3.1% at 8 h and reached maximal enrichment of 7.6% at 18 h. The (13)C enrichment of milk cis-9, trans-11 CLA reached a maximum of 0.4% at 18 h, confirming its conversion of VA to the Delta9-desaturase enzyme product. In the subjects examined, a portion (<10%) of the cis-9, trans-11 CLA present in milk was endogenously synthesized from VA. [ABSTRACT FROM AUTHOR]

Many clinical studies report that (n-3) PUFAs decrease the incidence of sudden death in patients with coronary artery disease after myocardial infarction (MI). However, the mechanisms for the beneficial effects of (n-3) PUFAs are unknown. The objectives of the present study were to confirm the findings from clinical trials using an animal model of MI in which dietary intake could be closely controlled and to utilize the model to investigate molecular mechanisms for the beneficial effects of (n-3) PUFAs. Male rats were subjected to coronary ligation to induce MI and were randomly assigned to diets high in (n-6) (58% of lipid) or (n-3) (28% of lipid) PUFAs for 6 mo. A diet high in (n-3) PUFAs was associated with an improvement in 6-mo survival (89.2% vs. 64.9%, P = 0.013) compared with rats consuming a diet high in (n-6) PUFAs (n = 37/group). In a separate study (n = 5 rats/diet group), the (n-3) PUFA diet decreased the (n-6):(n-3) PUFA ratio in plasma (0.6 +/- 0.1 vs. 7.9 +/- 1.8, P < 0.05) and cardiac tissue (0.9 +/- 0.1 vs. 11.8 +/- 1.6, P < 0.05) of rats fed for 4 wk. The increased survival in the (n-3) diet group was associated with decreased cardiac activities of protein kinase A and calcium calmodulin-dependent kinase II by 33-38% (P < 0.05) and a 28% decrease (P < 0.05) in phosphorylation (activation) of the ryanodine receptor calcium release channel. Based upon our results, we speculate that decreased activities of protein kinases induced by diets high in (n-3) PUFAs are associated with a decrease in sudden death after MI in rats. [ABSTRACT FROM AUTHOR]

To date, no studies have compared the effects of consuming a low-fat diet and a high monounsaturated fatty acid (MUFA) diet, under unrestricted energy intake conditions, on plasma C-reactive protein (CRP) concentrations. Men [n = 61; 37.5 +/- 11.5 y old (mean +/- SD), mean BMI 29.0 +/- 5.0 kg/m2] were randomly assigned to consume ad libitum a moderately low-fat diet (25.8% of energy intake from fat) or a high-fat diet rich in MUFA (40.1% of energy intake from fat, 22.5% from MUFA) for 6-7 wk. Plasma CRP concentrations were measured using a highly sensitive assay. Neither diet affected the plasma CRP concentration. However, baseline CRP concentrations predicted lipoprotein/lipid responsiveness to the experimental diets. After intake of the low-fat diet, plasma total and VLDL-triglyceride (TG) concentrations were increased in the subgroup with high CRP concentrations (P < 0.05 and P < 0.01, respectively) whereas they were reduced in the subgroup with low CRP concentrations at baseline (P < 0.01 for both). The high-MUFA diet reduced plasma TG, VLDL-TG, and VLDL cholesterol only in the subgroup with low CRP at baseline (P < 0.0001). In conclusion, the low-fat diet and the high-MUFA diet did not affect plasma CRP concentrations. However, baseline plasma CRP concentrations may modulate the diet-induced changes in plasma lipid and lipoprotein concentrations. [ABSTRACT FROM AUTHOR]

The dietary-induced changes in the fatty acid composition of plasma, platelet, and erythrocyte lipids were measured as a function of time. Healthy adults consumed a diet rich in saturated fat (18% total energy, TE) for 19 d and then crossed over, without washout, to a diet rich in (n-6) polyunsaturated fat (10% TE) for a further 19 d. The fatty acid composition of plasma and blood cell lipids was measured in blood samples collected from fasting subjects on d 0, 1, 2, 5, 8, 12, and 19 of consuming the diet rich in (n-6) polyunsaturated fats. The linoleic acid composition of all plasma, platelet, and erythrocyte lipids increased to a plateau within 19 d, reaching at least 70% of maximum within 5 d. The maximum increase in linoleic acid composition of erythrocyte phosphatidylcholine was 3.8 mol% at d 12; the increase at d 1 was 2 mol% and at d 5 was 3.2 mol%. The decrease in pentadecanoic acid composition followed a similar time course in all lipids with the exception of plasma phospholipids. Our results show that the time course of dietary-induced changes in erythrocyte fatty acid composition is similar to that in plasma and platelet lipids. These results provide convincing, albeit indirect evidence that the exchange of fatty acids from plasma to erythrocytes and platelets is a major determinant of their membrane fatty acid composition. [ABSTRACT FROM AUTHOR]

Proportions of vaccenic (trans-11 18:1) and rumenic (cis-9, trans-11 18:2) acids in mesenteric adipose, subcutaneous adipose, and longissimus muscle tissue lipids from lambs fed varying proportions of forages and concentrates were used to develop a mathematical model to predict exogenous and endogenous contributions to rumenic acid (RA) in the several tissues. From the model, we were able to estimate the proportion of absorbed RA, the proportion of vaccenic acid (VA) desaturated, the original proportion of VA in the tissue (before desaturation), and finally the proportion of RA synthesized endogenously. Estimates of endogenous RA were in the range of published data estimated by independent procedures. An independent data set of VA and RA in milk fat was used to challenge the model. Predictions were concordant with observations, although estimates of endogenous RA synthesis were lower than previous reports. Changing the amount of exogenous RA through manipulation of the diet influenced desaturation of VA inversely, so that endogenous RA synthesis was decreased when exogenous supply was increased (r = -0.80). The model should be challenged with data from human and nonruminant, as well as ruminant studies. [ABSTRACT FROM AUTHOR]

The objective of this study was to compare the effects of conjugated linoleic acid (CLA) as triacylglycerols (TAG) or free fatty acids (FFA) on body composition and energy balance in mice. We fed four groups of 5-wk-old Balb-C mice (n = 9) semipurified diets containing either CLA (0.5 g CLA/100 g of diet) or high oleic sunflower oil (HOSF) in the form of FFA or TAG for 42 d. Body composition was determined and the energy in the carcasses, excreta and food was measured in a bomb calorimeter. The amount of body fat was 4.72 +/- 0.95 g (17.9 +/- 2.8%) in the HOSF-FFA group, 2.36 +/- 0.29 g (9.4 +/- 1.0%) in the CLA-FFA mice (mean +/- SD, P < 0.05), 4.76 +/- 0.74 g (18.2 +/- 2.2%) in the HOSF-TAG group and 2.32 +/- 0.38 g (9.3 +/- 1.1%) in the CLA-TAG mice (P < 0.05). The percentage of energy intake that was stored in the body was 3.5 +/- 1.2% in the HOSF-FFA group, 0.6 +/- 0.3% in the CLA-FFA group (P < 0.05), 3.5 +/- 1.1% in the HOSF-TAG group and 0.5 +/- 0.4 in the CLA-TAG mice (P < 0.05). Conversely, the percentage of energy intake that was expended as heat was 89.4 +/- 1.2% in the HOSF-FFA group, 92.4 +/- 0.8% in the CLA-FFA mice (P < 0.05), 89.47 +/- 1.23% in the HOSF-TAG group and 92.2 +/- 0.4% in the CLA-TAG group (P < 0.05). Thus, CLA in the form of FFA or TAG had similar effects on body composition and energy balance. [ABSTRACT FROM AUTHOR]

The present study was designed to examine the effects of increasing dietary levels of vaccenic acid (VA) and cis-9, trans-11 conjugated linoleic acid (CLA) on chemically induced mammary carcinogenesis in rats. Both fatty acids were provided as a natural component in butter fat. The conversion of VA to CLA by delta9-desaturase was documented previously in several species, including rats and humans. Specifically, our objective was to determine the relative contribution of dietary VA and CLA to the tissue concentration of CLA and its ability to inhibit the development of mammary carcinomas. A total of 7 diets were formulated with varying levels of CLA and VA. The overall dietary treatment scheme was designed to evaluate the modulation of mammary cancer risk by 1). small increases of CLA in the presence of a low level of VA and 2). more substantial increases of VA against a background of low levels of CLA. As expected, small increases in dietary CLA at the low end of the CLA dose-response range did not reduce tumorigenesis. In contrast, there was a distinct and marked inhibitory response to VA that was dose dependent. The effect of VA was magnified in this experiment because the dose range of VA tested was much broader than that of CLA. Fatty acid analysis showed that the conversion of dietary VA to CLA resulted in a dose-dependent increase in the accumulation of CLA in the mammary fat pad, which was accompanied by a parallel decrease in tumor formation in the mammary gland. The finding confirms that the conversion of VA to CLA is as important for cancer prevention as the dietary supply of CLA. Thus, VA is also anticarcinogenic, and VA and CLA represent functional food components that are present in ruminant fat. [ABSTRACT FROM AUTHOR]

The objective of this study was to assess the relative long-term effects of linoleic (cis, cis 18:2), linolelaidic (trans, trans 18:2), and palmitic (16:0) acids on hepatic lipoprotein production in HepG2 cells. All fatty acids increased the mass of triglycerides (TG) in the medium and the incorporation of [(3)H]-glycerol into secreted TG; the increase was more pronounced with linoleic acid than with linolelaidic and palmitic acids. The net accumulation in the medium of apolipoprotein (apo) A-I was not affected by the fatty acids tested and moderate changes in that of apoB resulted in apoB/apoA-I mass ratios of 1.05, 1.27 and 0.86 with linoleic, linolelaidic and palmitic acids, respectively. The incorporation of [(14)C]-acetate into cellular plus secreted total sterols was 9.1%, 33.6% and 17.4% of total [(14)C]-labeled lipids with linoleic, linolelaidic and palmitic acids, respectively. Relative to linoleic acid, palmitic acid, and to a greater extent (P < 0.05) linolelaidic acid, increased the secretion and cellular accumulation of [(14)C]-labeled free cholesterol (FC) and cholesteryl esters and decreased those of TG and phospholipids (PL). Compared with linoleic acid, linolelaidic acid increased LDL-cholesterol (C) and HDL-C by 154% (P < 0.001) and 50% (P = 0.016), respectively, whereas palmitic acid increased LDL-C by 17% (P > 0.1) and did not affect HDL-C. The LDL-C to HDL-C ratios were 0.70, 1.18 and 0.96 with linoleic, linolelaidic and palmitic acids, respectively. These differences were not due to altered LDL receptor activity. The PL to C ratios of HDL particles were 1.61, 0.40 and 0.77 with linoleic acid, linolelaidic acid and palmitic acid, respectively. These results suggest that relative to cis polyunsaturated and saturated fatty acids, trans PUFA more adversely affect the concentration and composition of apoA-I- and apoB-containing lipoproteins secreted by HepG2 cells. [ABSTRACT FROM AUTHOR]

The presence of medium-chain fatty acids in dietary fatty acid as well as the triacylglycerol structure may influence the absorption and lymphatic transport of fatty acids. We compared the lymphatic transport and recovery of fatty acids from four intragastrically administered fats based on rapeseed oil and decanoic acid in two rat models of normal absorption and malabsorption, respectively. The fats were: 1) a fat with a regiospecific structure, 2) a similar fat but with a random distribution of fatty acids in the triacylglycerol molecule, 3) a physical mixture of tridecanoin and rapeseed oil and 4) rapeseed oil as control. Lymph samples were collected for 24 h. Significantly higher recoveries were observed of total fatty acids, oleic acid, linoleic acid and linolenic acid from the specific oil in malabsorbing rats and of linoleic acid in normal rats fed specific oil compared with those fed rapeseed oil. Furthermore, the recoveries of oleic acid and linolenic acid from the specific oil in normal rats were higher than those from the other oils. In malabsorbing rats, the transport of all fats was approximately 90% less than that of normal rats. The present study demonstrates improved hydrolysis and absorption of the specific oil compared with the other oils examined both in rats with normal absorption and in rats with malabsorption. [ABSTRACT FROM AUTHOR]

Lipid added to animal diets can affect productive efficiency through a combination of caloric and regulatory effects. Any attempt to improve productive efficiency of ruminants by modifying the amount or composition of lipid added to the diet must take into account ruminal metabolism of lipids. The caloric value of lipid is changed little as it passes through the rumen, but the greater concern is the possible negative effect of lipid on the energy value of the basal diet. Limiting unsaturated fatty acids fed to ruminants to just a few percent of the diet to avoid digestive disturbances, combined with extensive hydrogenation by ruminal microbes, maintains only small quantities of unsaturated fatty acids in duodenal contents. However, in some studies, lipid added to ruminant diets has invoked metabolic changes that were not attributable to caloric effects. These metabolic changes suggest that the rumen does not maintain digesta flow with constant lipid composition in all circumstances. Variations in rumen outflow of biohydrogenation intermediates and microbial lipids are as great, or greater in some situations, than unsaturated fatty acids. Diet characteristics, such as amount of grain or unsaturated lipid, can substantially alter the nature of fatty acids absorbed from the duodenum and deposited in animal tissues. [ABSTRACT FROM AUTHOR]