Plasma Concentrations Of Fatty Acids Research Articles

Alpha-Lipoic Acid Alleviates Acute Inflammation and Promotes Lipid Mobilization During the Inflammatory Response in White Adipose Tissue of Mice.

Recently, white adipose tissue has been shown to exhibit immunological activity, and may play an important role in host defense and protection against bacterial infection. Αlpha-lipoic acid (α-LA) has been demonstrated to function as an anti-inflammatory and anti-oxidant agent. However, its influence on the inflammatory response and metabolic changes in white adipose tissue remains unknown. We used male C57BL/6 mice as models to study the effect of α-LA on the inflammatory response and metabolic changes in white adipose tissue after stimulation with lipopolysaccharide (LPS). The non-esterified fatty acid content was measured by an automatic biochemical analyzer. The expression of inflammation-, lipid- and energy metabolism-related genes and proteins was determined by quantitative real-time polymerase chain reaction and western blotting. The results indicated that α-LA significantly decreased the epididymis fat weight index and the non-esterified fatty acid content in plasma compared with the control group. LPS significantly increased the expression of inflammation genes and α-LA reduced their expression. The LPS-induced expression of nuclear factor-κB protein was decreased by α-LA. Regarding lipid metabolism, α-LA significantly counteracted the inhibitory effects of LPS on the expression of hormone-sensitive lipase gene and protein. α-LA evidently increased the gene expression of fatty acid transport protein 1 and cluster of differentiation 36. Regarding energy metabolism, α-LA significantly increased the expression of most of mitochondrial DNA-encoded genes compared with the control and LPS group. Accordingly, α-LA can alleviate acute inflammatory response and this action may be related with the promotion of lipid mobilization in white adipose tissue.

Using a lipidomics approach for nutritional phenotyping in response to a test meal containing gamma-linolenic acid

Plasma fatty acids are derived from preformed sources in the diet and de novo synthesis through the action of desaturase and elongase enzymes. This study was designed to examine the elongation of gamma-linolenic acid (GLA, 18:3n6) into dihomo-gamma-linolenic acid (DGLA, 20:3n6) over an 8-h period using both targeted gas chromatography–flame ionization detection and untargeted liquid chromatography–mass spectrometry-based lipidomics utilizing the sequential window acquisition of all theoretical fragment-ion spectra (SWATH). In a single blind, placebo-controlled, crossover design, seven healthy subjects consumed a test meal that consisted of GLA fat (borage oil) or a control fat (a mixture of corn, safflower, sunflower and extra-virgin light olive oils) on three separate test days for each test meal. Total plasma fatty acid concentrations and 366 unique lipid species were measured at 0, 2, 4, 6 and 8 h in response to the test meals. Mean plasma 18:3n6 was 7-fold higher to the GLA challenge compared with baseline and the control meal. By 8 h, mean plasma 20:3n6 was significantly higher in response to the GLA test meal than baseline and the control group. Five of the seven subjects were “responders” in converting GLA into DGLA, but two subjects did not show this conversion. The conversion was independent of physical activity level. Using polyunsaturated fatty acid metabolism as an example, this study demonstrates inter-individual differences in enzymatic capacities to inform exact nutritional and metabolic phenotyping that could be used for precision medicine.

Altered plasma levels of decanoic acid in colorectal cancer as a new diagnostic biomarker.

Colorectal cancer (CRC) is one of the most common tumors in developed countries. The five-year survival rate decreases depending on how advanced the CRC is when first diagnosed. Screening has been proven to greatly reduce mortality from colorectal cancer, but an ideal screening tool is far from being established. Here, we aimed to discover and validate early CRC biomarkers by means of an untargeted/targeted metabolomic approach. A preliminary untargeted analysis of plasma lipids performed on a small patient cohort (30 plasma samples) revealed some alterations that occurred in the presence of this tumor. In particular, medium-chain fatty acids with between six and twelve carbon atoms (C6-C12) were found to be the lipid class that showed the most marked changes upon the development of CRC. In order to evaluate the utility of this lipid class as diagnostic CRC biomarkers, a further study based on a wider cohort of patients (117 plasma samples) was performed. Using a targeted approach, these fatty acids were quantified in plasma samples by means of fast gas chromatography coupled to a time-of-flight analyzer. Plasma samples from patients with CRCs at different tumor stages were analyzed and compared to those from healthy subjects, ulcerative colitis patients, high-grade dysplasia adenoma patients, and breast cancer patients in order to test the specificity and sensitivity of these possible biomarkers. Results revealed significant differences among the considered groups in terms of their C6, C8, C10, and C12 fatty acid plasma concentrations. In particular, receiver operating characteristic (ROC) curves obtained for the C10 fatty acid gave an area under the curve of 0.8195 along with a sensitivity of 87.8% and a specificity of 80%, strongly suggesting that it could be a valuable early diagnostic biomarker of CRC.

Fatty Acid Composition in Feeds and Plasma of Canadian Premature Infants.

The objective of the present exploratory study was to investigate how the fatty acid (FA) composition of different food sources for preterm infants including breast milk (BM), formula (F), human milk fortifiers (HMFs), and total parenteral nutrition (TPN) impacted preterm infant's plasma FA. The associations between FA content of plasma with antioxidant enzyme activity and cognition were also evaluated. Thirty-two premature infants were included in the present study. Five different feeds (BM, F, BM + F, BM + HMF, and TPN) were provided. Foods and preterm infant plasma samples were collected at the same time on the same day biweekly where possible. Separation and identification of the plasma and food FA methyl esters were performed by gas-liquid chromatography. Antioxidant enzymes were measured. The Bayley Scale of Infant Development version III was used to evaluate cognition. In food sources, BM contained significantly lower stearic acid (C18:0) (P < 0.05), oleic acid (C18:1n9) (P < 0.01), linoleic acid (C18:2n6) (P < 0.01), α-linoleic acid (C18:3n3) (P < 0.01), and arachidonic acid (C20:4n6) (P < 0.05) compared with the F. Palmitic acid (C16:0) was significantly higher (P < 0.05) in the BM + HMF compared with the BM. Stearic acid (C18:0) was significantly higher (P < 0.05) in the BM + F and BM + HMF compared with the BM. In the plasma lauric acid (C12:0) (P < 0.05) and myristic acid (C14:0) (P < 0.001) were higher in the BM-fed babies compared with the F-fed or TPN-recipient groups. Antioxidant enzymes, activities and cognition scores did not differ by feeding groups, however the study may not have been powered to detect these differences. The type, and therefore quality, of fatty acids is an important consideration when selecting what is fed to premature infants because differences in feed fatty acids were seen in some plasma fatty acids in the study.

Maternal Plasma DHA Levels Increase Prior to 29 Days Post-LH Surge in Women Undergoing Frozen Embryo Transfer: A Prospective, Observational Study of Human Pregnancy.

Docosahexaenoic acid (DHA) is an important fatty acid required for neurological development but its importance during early fetal neurological organogenesis is unknown. This study aimed to assess plasma fatty acid changes in early pregnancy in women undergoing natural cycle-frozen embryo transfer as a means of achieving accurately timed periconceptual sampling. Women undergoing frozen embryo transfer were recruited and serial fasting blood samples were taken pre-luteinizing hormone (LH) surge, and at 18, 29, and 45 d post-LH surge and fatty acids were analyzed using gas chromatography. This study took place at the Assisted Conception Unit, Glasgow Royal Infirmary, Scotland. Plasma fatty acid concentrations and influence of twin pregnancies on DHA plasma concentration were measured. In pregnant women, there was a rapid, early increase in the maternal rate of change of plasma DHA concentration observed by 29 d post-LH surge (mean ± SD, from 0.1 ± 1.3 to 1.6 ± 2.9 nmol DHA per mL plasma per day). This early pressure to increase plasma DHA concentration was further emphasized in twin pregnancies where the increase in DHA concentration over 45 d was 2-fold higher than in singleton pregnancies (mean ± SD increase, 74 ± 39 nmol/mL vs 36 ± 40 nmol/mL). An index of delta-6 desaturase activity increased 30% and positively correlated with the rate of change of DHA concentration between 18 and 29 d post-LH surge (R2 adjusted = 41%; P = .0002). DHA was the only fatty acid with a continual accelerated increase in plasma concentration and a positive incremental area under the curve (mean ± SD, 632 ± 911 nmol/mL × d) during the first 45 d of gestation. An increase in maternal plasma DHA concentration is initiated in human pregnancy prior to neural tube closure which occurs at 28 d gestation.

Acculturation and Plasma Fatty Acid Concentrations in Hispanic and Chinese-American Adults: The Multi-Ethnic Study of Atherosclerosis.

BackgroundAcculturation to the U.S. is associated with increased risk of cardiovascular disease, but the etiologic pathways are not fully understood. Plasma fatty acid levels exhibit ethnic differences and are emerging as biomarkers and predictors of cardiovascular disease risk. Thus, plasma fatty acids may represent one pathway underlying the association between acculturation and cardiovascular disease. We investigated the cross-sectional relationship between acculturation and plasma phospholipid fatty acids in a diverse sample of Hispanic- and Chinese-American adults.Methods and FindingsParticipants included 377 Mexican, 320 non-Mexican Hispanic, and 712 Chinese adults from the Multi-Ethnic Study of Atherosclerosis, who had full plasma phospholipid assays and acculturation information. Acculturation was determined from three proxy measures: nativity, language spoken at home, and years in the U.S., with possible scores ranging from 0 (least acculturated) to 5 (most acculturated) points. α-Linolenic acid, linoleic acid, eicosapentaenoic acid, docosahexaenoic acid, and arachidonic acid were measured in fasting plasma. Linear regression models were conducted in race/ethnicity-stratified analyses, with acculturation as the predictor and plasma phospholipid fatty acids as the outcome variables. We ran secondary analyses to examine associations between acculturation and dietary fatty acids for comparison. Covariates included age, gender, education, and income. Contrary to our hypothesis, no statistically significant associations were detected between acculturation and plasma phospholipid fatty acids for Chinese, non-Mexican Hispanic, or Mexican participants. However, acculturation was related to dietary total n-6 fatty acids and dietary n-3/n-6 ratios in expected directions for Mexican, non-Mexican Hispanic, and combined Hispanic participants. In Chinese individuals, acculturation was unexpectedly associated with lower arachidonic acid intake.ConclusionAbsence of associations between acculturation and plasma phospholipid fatty acids suggests that changes in the plasma phospholipid fatty acids studied do not account for the observed associations of acculturation to the U.S. and cardiovascular disease risk. Similar findings were observed for eicosapentaenoic acid and docosahexaenoic acid, when using dietary intake. However, the observed associations between dietary n-6 fatty acids and acculturation in Hispanic individuals suggest that dietary intake may be more informative than phospholipids when investigating acculturation effects. In Chinese individuals, acculturation may have a possible protective effect through decreased arachidonic acid intake. Further research on dietary fatty acids and other cardiovascular disease biomarkers is needed to identify possible etiologic mechanisms between acculturation and cardiovascular disease.

Effects of replacing ground corn with wet brewers grains on growth performance and concentrations of liver trace minerals and plasma fatty acids of preconditioning beef heifers fed medium-quality fescue hay

ABSTRACT Our goal was to evaluate growth performance and concentrations of liver trace minerals and plasma fatty acids of beef heifers supplemented with wet brewers grains (WBG) replacing ground corn (CN). On d 0, 27 Angus beef heifers (218 ± 3 kg; 225 ± 23 d of age) were randomly assigned into 1 of 9 drylot pens (3 heifers per pen). Treatments were randomly assigned to pens (3 pens per treatment) and consisted of heifers receiving a 42-d period of daily supple- mentation 'with 100% CN, 100% WBG, or a 50:50 mixture of CN and WBG (CNWBG). Supplements provided equal daily supplemental TDN (0.7% of BW). Average daily gain from d 0 to 42 was similar (P = 0.65) between CNWBG and WBG, and tended (P ≤ 0.08) to be least for CN. Hay and total DMI were less (P ≤ 0.05) for heifers fed WBG versus CN and CNWBG supplements in 3 of 6 wk. Thus, G:F was similar (P = 0.63) between CNWBG and WBG but least (P ≤ 0.004) for CN heifers. Intake of S, Cu, Se, and Zn increased (P ≤ 0.05) as WBG replaced corn. Yet, liver concentrations of trace minerals did not differ among treatments (P ≥ 0.16). Intake of supplemental fat and total fat increased (P ≤ 0.02) as WBG replaced corn. Plasma 18:1 trans-11 and 18:1 cis-9 concentrations were less for WBG versus CN and CNWNG heifers (P ≤ 0.04). Therefore, replacing ground corn with WBG enhanced growth performance but not concentrations of plasma fatty acids and liver trace mineral in beef heifers.

Effects of a docosahexaenoic acid-rich microalgae nutritional product on insulin sensitivity after prolonged dexamethasone treatment in healthy mature horses.

To determine effects of a microalgae nutritional product on insulin sensitivity in horses. 8 healthy mature horses. PROCEDURES :Horses (n = 4/group) received a basal diet without (control diet) or with docosahexaenoic acid-rich microalgae meal (150 g/d) for 49 days (day 0 = first day of diet). On day 28, an isoglycemic hyperinsulinemic clamp procedure was performed. Horses then received dexamethasone (0.04 mg/kg/d) for 21 days. On day 49, the clamp procedure was repeated. After a 60-day washout, horses received the alternate diet, and procedures were repeated. Plasma fatty acid, glucose, and insulin concentrations and glucose and insulin dynamics during the clamp procedure were measured on days 28 and 49. Two estimates of insulin sensitivity (reciprocal of the square root of the insulin concentration and the modified insulin-to-glucose ratio for ponies) were calculated. Baseline glucose and insulin concentrations or measures of insulin sensitivity on day 28 did not differ between horses when fed the control diet or the basal diet plus microalgae meal. On day 49 (ie, after dexamethasone administration), the microalgae meal was associated with lower baseline insulin and glucose concentrations and an improved modified insulin-to-glucose ratio for ponies, compared with results for the control diet. Although the microalgae meal had no effect on clamp variables following dexamethasone treatment, it was associated with improved plasma glucose and insulin concentrations and insulin sensitivity estimates. A role for microalgae in the nutritional management of insulin-resistant horses warrants investigation.

Brain Arachidonic Acid Incorporation and Turnover are not Altered in the Flinders Sensitive Line Rat Model of Human Depression.

Brain serotonergic signaling is coupled to arachidonic acid (AA)-releasing calcium-dependent phospholipase A2. Increased brain serotonin concentrations and disturbed serotonergic neurotransmission have been reported in the Flinders Sensitive Line (FSL) rat model of depression, suggesting that brain AA metabolism may be elevated. To test this hypothesis, (14)C-AA was intravenously infused to steady-state levels into control and FSL rats derived from the same Sprague-Dawley background strain, and labeled and unlabeled brain phospholipid and plasma fatty acid concentrations were measured to determine the rate of brain AA incorporation and turnover. Brain AA incorporation and turnover did not differ significantly between controls and FSL rats. Compared to controls, plasma unesterified docosahexaenoic acid was increased, and brain phosphatidylinositol AA and total lipid linoleic acid and n-3 and n-6 docosapentaenoic acid were significantly decreased in FSL rats. Several plasma esterified fatty acids differed significantly from controls. In summary, brain AA metabolism did not change in FSL rats despite reported increased levels of serotonin concentrations, suggesting possible post-synaptic dampening of serotonergic neurotransmission involving AA.

Genetic and epigenetic transgenerational implications related to omega-3 fatty acids. Part I: maternal FADS2 genotype and DNA methylation correlate with polyunsaturated fatty acid status in toddlers: an exploratory analysis

Polyunsaturated fatty acid metabolism in toddlers is regulated by a complex network of interacting factors. The contribution of maternal genetic and epigenetic makeup to this milieu is not well understood. In a cohort of mothers and toddlers 16 months of age (n = 65 mother-child pairs), we investigated the association between maternal genetic and epigenetic fatty acid desaturase 2 (FADS2) profiles and toddlers' n-6 and n-3 fatty acid metabolism. FADS2 rs174575 variation and DNA methylation status were interrogated in mothers and toddlers, as well as food intake and plasma fatty acid concentrations in toddlers. A multivariate fit model indicated that maternal rs174575 genotype, combined with DNA methylation, can predict α-linolenic acid plasma concentration in all toddlers and arachidonic acid concentrations in boys. Arachidonic acid intake was predictive for its plasma concentration in girls, whereas intake of 3 major n-3 species (eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids) were predictive for their plasma concentrations in boys. FADS2 genotype and DNA methylation in toddlers were not related to plasma concentrations or food intakes, except for CpG8 methylation. Maternal FADS2 methylation was a predictor for the boys' α-linolenic acid intakes. This exploratory study suggests that maternal FADS2 genetic and epigenetic status could be related to toddlers' polyunsaturated fatty acid metabolism.

Circulating profiling reveals the effect of a polyunsaturated fatty acid-enriched diet on common microRNAs

BackgroundConsumption of long-chain polyunsaturated fatty acids (PUFAs), which are abundant in seafood and nuts, ameliorates components of the metabolic syndrome. Circulating microRNAs (miRNAs) have demonstrated to be valuable biomarkers of metabolic diseases. Here, we investigated whether a sustained nuts-enriched diet can lead to changes in circulating miRNAs, in parallel to the dietary modification of fatty acids (FAs). Methods and ResultsThe profile of 192 common miRNAs was assessed (TaqMan low-density arrays) in plasma from 10 healthy women before and after an 8-week trial with a normocaloric diet enriched with PUFAs (30 g/day of almonds and walnuts). The most relevant miRNAs were validated in an extended sample of 30 participants (8 men and 22 women). Adiponectin was measured by immunoassay and FAs by gas liquid chromatography coupled to mass spectrometry. The percentage of both ω-3 (P=.01) and ω-6 (P=.029) PUFAs of dietary origin (as inferred from plasma FA concentrations) increased, whereas saturated FAs decreased (P=.0008). Concomitantly with changes in circulating FAs, several miRNAs were modified by treatment, including decreased miR-328, miR-330-3p, miR-221 and miR-125a-5p, and increased miR-192, miR-486-5p, miR-19b, miR-106a, miR-769-5p, miR-130b and miR-18a. Interestingly, miR-106a variations in plasma correlated with changes in PUFAs, while miR-130b (r=0.58, P=.003) and miR-221 (r=0.46, P=.03) reflected changes in C-reactive protein. The dietary modulation of miR-125a-5p mirrored changes in fasting triglycerides (r=−0.44, P=.019) and increased adiponectin (r=0.43, P=.026). ConclusionDietary FAs (as inferred from plasma FA concentration) are linked to changes in circulating miRNAs, which may be modified by a PUFAs-enriched diet.

Liver Disease, Systemic Inflammation, and Growth Using a Mixed Parenteral Lipid Emulsion, Containing Soybean Oil, Fish Oil, and Medium Chain Triglycerides, Compared With Soybean Oil in Parenteral Nutrition-Fed Neonatal Piglets.

The optimal parenteral lipid emulsion for neonates should reduce the risk of intestinal failure-associated liver disease and inflammation, while supporting growth and development. This could be best achieved by balanced content of ω-6 and ω-3 polyunsaturated fatty acids (PUFAs). Using a neonatal piglet model of parenteral nutrition (PN), we compared a 100% soy oil-based emulsion (ω-6:ω-3 PUFA: 7:1) with a mixed lipid emulsion comprising 30% soy oil, 30% medium-chain triglycerides, 25% olive oil, and 15% fish oil (ω-6:ω-3 PUFA: approximately 2.5:1) with regard to liver disease, inflammation, and fatty acid content in plasma and brain. Neonatal piglets, 3-6 days old, underwent jugular catheter insertion for isonitrogenous, isocaloric PN delivery over 14 days. The IL group (n = 8) was treated with Intralipid; the ML group (n = 10) was treated with the mixed lipid (SMOFlipid). Bile flow, liver chemistry, C-reactive protein (CRP), and PUFA content in plasma phospholipids and brain were compared. Compared with the IL group, ML-treated piglets had increased bile flow (P = .008) and lower total bilirubin (P = .001) and CRP (P = .023) concentrations. The ω-6 long-chain PUFA content was lower in plasma and brain for the ML group. The key ω-3 long-chain PUFA for neonatal development, docosahexaenoic acid (DHA), was not different between groups. The mixed lipid, having less ω-6 PUFA and more ω-3 PUFA, was able to prevent liver disease and reduce systemic inflammation in PN-fed neonatal piglets. However, this lipid did not increase plasma or brain DHA status, which would be desirable for neonatal developmental outcomes.

Plasma elaidic acid level as biomarker of industrial trans fatty acids and risk of weight change: report from the EPIC study.

BackgroundFew epidemiological studies have examined the association between dietary trans fatty acids and weight gain, and the evidence remains inconsistent. The main objective of the study was to investigate the prospective association between biomarker of industrial trans fatty acids and change in weight within the large study European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.MethodsBaseline plasma fatty acid concentrations were determined in a representative EPIC sample from the 23 participating EPIC centers. A total of 1,945 individuals were followed for a median of 4.9 years to monitor weight change. The association between elaidic acid level and percent change of weight was investigated using a multinomial logistic regression model, adjusted by length of follow-up, age, energy, alcohol, smoking status, physical activity, and region.ResultsIn women, doubling elaidic acid was associated with a decreased risk of weight loss (odds ratio (OR) = 0.69, 95% confidence interval (CI) = 0.55-0.88, p = 0.002) and a trend was observed with an increased risk of weight gain during the 5-year follow-up (OR = 1.23, 95% CI = 0.97-1.56, p = 0.082) (p-trend<.0001). In men, a trend was observed for doubling elaidic acid level and risk of weight loss (OR = 0.82, 95% CI = 0.66-1.01, p = 0.062) while no significant association was found with risk of weight gain during the 5-year follow-up (OR = 1.08, 95% CI = 0.88-1.33, p = 0.454). No association was found for saturated and cis-monounsaturated fatty acids.ConclusionsThese data suggest that a high intake of industrial trans fatty acids may decrease the risk of weight loss, particularly in women. Prevention of obesity should consider limiting the consumption of highly processed foods, the main source of industrially-produced trans fatty acids.

Comprehensive profiling of plasma fatty acid concentrations in young healthy Canadian adults.

Circulating fatty acids (FA) are associated with a multitude of chronic diseases. However, a major gap in establishing such relationships is the lack of accepted fatty acid reference ranges representing healthy individuals. Data on validated FA reference ranges would provide a better understanding of study baseline measures and aid in the evaluation and interpretation of pharmaceutical or dietary interventions. Reference ranges for plasma FA levels have been reported in a few small studies and on a limited number of FA. Therefore, we determined the average and percentiles of a broad set of 61 FA (C14 - C24:1) from plasma total lipids from an ethnically diverse population of healthy young Canadian males and females (Total n = 826). Plasma concentrations of some of the major FA ranged from 0.3 to 4.1 mmol/L for palmitic acid, 0.1 to 1.0 mmol/L for stearic acid, 0.03 to 3.2 mmol/L for oleic acid, 0.2 to 5.0 mmol/L for linoleic acid (LA), 12.0 to 186.9 μmol/L for α-linolenic acid, and 7.2 to 237.5 μmol/L for docosahexaenoic acid (DHA). Males had significantly higher plasma concentrations of γ-linolenic acid (GLA) and n-3 docosapentaenoic acid and lower concentrations of palmitoleic acid, LA and DHA than females. Comparison of FA concentrations between Caucasians, East Asians and South Asians revealed that South Asians had significantly lower levels of palmitoleic acid (p < 0.01) and oleic acid (p = 0.01) while East Asians had lower levels of GLA (p = 0.02) and dihomo-γ-linolenic acid (p = 0.03). Overall, these data provide a comprehensive set of quantitative values that profiles a small cohort of Canadians which highlights the utility of establishing validated FA reference ranges that may be used to understand how deficient, suboptimal, or excess amounts of a given FA may be associated with chronic disease.

Platelet Arachidonic Acid Deficiency May Contribute to Abnormal Platelet Function During Parenteral Fish Oil Monotherapy in a Piglet Model.

Fish oil monotherapy has been an advance for treating intestinal failure-associated liver disease (IFALD). However, such patients are at risk of bleeding complications from liver disease and because fish oil can inhibit thrombosis. We have previously reported abnormal platelet function in neonatal piglets given fish oil monotherapy during parenteral nutrition (PN). The purpose of this study was to determine if abnormal fatty acid composition of the platelets could explain the prior observed antiplatelet effect. Neonatal piglets were assigned to 2 treatments: PN with fish oil monotherapy (FO; n = 4) or PN with soy oil (SO; n = 5). On day 14, plasma was collected and platelets isolated by centrifuging. The fatty acid content in plasma and platelet plug were measured using gas liquid chromatography and compared with controls (CON; n = 5). The arachidonic acid (AA) content in the FO group was on average half that of the SO group, in both the platelets (FO, 3.5% vs SO, 7.6%; P = .021; CON, 4.5%-11%) and the plasma (FO, 3.8% vs SO, 9.2%; P = .002; CON, 6.1%-9.5%). No bleeding complications were observed for any piglets during PN treatment. Using platelet mapping, we have previously shown that neonatal piglets given fish oil monotherapy have abnormal platelet function in the AA pathway. This report demonstrates that such an abnormality can be explained by platelet AA deficiency. Platelet mapping and platelet fatty acid analysis should be undertaken in human infants treated with fish oil monotherapy during PN.

Insulin-independent regulation of hepatic triglyceride synthesis by fatty acids

A central paradox in type 2 diabetes is the apparent selective nature of hepatic insulin resistance--wherein insulin fails to suppress hepatic glucose production yet continues to stimulate lipogenesis, resulting in hyperglycemia, hyperlipidemia, and hepatic steatosis. Although efforts to explain this have focused on finding a branch point in insulin signaling where hepatic glucose and lipid metabolism diverge, we hypothesized that hepatic triglyceride synthesis could be driven by substrate, independent of changes in hepatic insulin signaling. We tested this hypothesis in rats by infusing [U-(13)C] palmitate to measure rates of fatty acid esterification into hepatic triglyceride while varying plasma fatty acid and insulin concentrations independently. These experiments were performed in normal rats, high fat-fed insulin-resistant rats, and insulin receptor 2'-O-methoxyethyl chimeric antisense oligonucleotide-treated rats. Rates of fatty acid esterification into hepatic triglyceride were found to be dependent on plasma fatty acid infusion rates, independent of changes in plasma insulin concentrations and independent of hepatocellular insulin signaling. Taken together, these results obviate a paradox of selective insulin resistance, because the major source of hepatic lipid synthesis, esterification of preformed fatty acids, is primarily dependent on substrate delivery and largely independent of hepatic insulin action.

Desaturation index versus isotopically measured de novo lipogenesis as an indicator of acute systemic lipogenesis.

BackgroundHigh carbohydrate feeding is known to increase plasma triglycerides as well as hepatic de novo lipogenesis (DNL) and may be implicated in the development of hepatic insulin resistance and fatty liver. Unfortunately, it is technically challenging to determine what proportion of circulating plasma triglycerides have been derived from the newly synthesized fatty acids in the postprandial period. The aims of this study were to 1) characterize the changes in the plasma postprandial total fatty acid pool in beagles following the consumption of meals containing 44% (Control) and 74% (High Sucrose) carbohydrate and 2) determine if changes in plasma fatty acid concentration and delta-9 desaturation index (DI) would be useful as simple and easy to measure biomarkers of systemic DNL.FindingsNo differences in plasma total palmitic acid (16:0), stearic acid (18:0) and oleic acid (18:1) concentrations or delta-9 DI for the total 18:0 and 18:1 pools between High Sucrose and Controls were observed. However, newly synthesized 16:0 (2.6 ± 0.2% vs. 8.8 ± 2.0%; p = 0.016), 18:0 (0.93 ± 0.2% vs. 4.1 ± 1.7%; p = 0.007) and 18:1 (0.29 ± 0.09% vs. 3.5 ± 1.2%; p = 0.017) were higher in High Sucrose versus Control animals, respectively. Also, the delta-9 DI for the newly synthesized 18:0 and 18:1 pools was higher at 2 and 6 hours postprandial, with a pattern of change which supports the increased stearoyl-CoA desaturase (SCD-1) activity following high carbohydrate feeding followed by a down regulation of this enzyme.ConclusionsOur data show that high sucrose meals increase the relative contribution of systemic DNL produced fatty acids to the total postprandial plasma fatty acid pool. These data also show that a different pattern of both fatty acid synthesis and disposal occurs depending on energy and macronutrient profile of the meal. These changes are in spite of no observable changes in the plasma concentrations or ratios of the total fatty acid pool opposed to the observed changes in the newly synthesized fatty acid pool.

Dietary and plasma fatty acid concentrations associated with processed red meat consumption

Dietary and plasma fatty acid concentrations associated with processed red meat consumption

110 BARLEY SUPPLEMENTATION AT MID-GESTATION IN BROODMARES DOES NOT AFFECT FETAL DEVELOPMENT AND IS ACCOMPANIED BY MINIMAL PLACENTAL ADAPTATIONS

Modifications of maternal environment could alter fetal growth and development through the placenta and thus health in adulthood. The developmental origins of health and disease suggest that maternal nutrition during pregnancy may affect offspring development and subsequent energy metabolism. To understand the effect of common feeding practices during gestation, 24 saddlebred mares were allocated to 1 of 2 groups: group B was supplemented twice a day with barley (B) and group F was fed only with fodder (F) between month 7 of gestation and foaling. B mares maintained an optimal body condition score through gestation, with an increase in glycaemia and insulinemia after each meal and insulin resistance in month 9 of gestation. F mares lost condition as assessed by body condition score in the last part of gestation, leading to a moderate undernutrition and a transitional increase in nonesterified fatty acid plasma concentrations. Diets had no effect on feto-placental biometry or on placental structure. In contrast, an increase in microcotyledonary vessel volume was observed in F placentas, indicating placental adaptation, possibly to increase fetomaternal exchanges. There was no overall difference in the expression of genes involved in vascularization, nutrient transfer, growth, and development between placentas from B and F mares. Nevertheless, as seen in other species, sex-specific effects of maternal nutrition were observed in placentas from female foals, with differences in the expression of endogline, kinase insert domain receptor, insulin-like growth factor 2 and insulin-like growth factor 1 receptor genes. This study demonstrates that breeding practices such as supplementation in concentrate at mid-gestation do not seem to affect fetal development. More work is ongoing to evaluate postnatal health.

Higher insulin-sensitizing response after sprint interval compared to continuous exercise.

This study investigated which exercise mode (continuous or sprint interval) is more effective for improving insulin sensitivity. Ten young, healthy men underwent a non-exercise trial (CON) and 3 exercise trials in a cross-over, randomized design that included 1 sprint interval exercise trial (SIE; 4 all-out 30-s sprints) and 2 continuous exercise trials at 46% VO2peak (CELOW) and 77% VO2peak (CEHIGH). Insulin sensitivity was assessed using intravenous glucose tolerance test (IVGTT) 30 min, 24 h and 48 h post-exercise. Energy expenditure was measured during exercise. Glycogen in vastus lateralis was measured once in a resting condition (CON) and immediately post-exercise in all trials. Plasma lipids were measured before each IVGTT. Only after CEHIGH did muscle glycogen concentration fall below CON (P<0.01). All exercise treatments improved insulin sensitivity compared with CON, and this effect persisted for 48-h. However, 30-min post-exercise, insulin sensitivity was higher in SIE than in CELOW and CEHIGH (11.5±4.6, 8.6±5.4, and 8.1±2.9 respectively; P<0.05). Insulin sensitivity did not correlate with energy expenditure, glycogen content, or plasma fatty acids concentration (P>0.05). After a single exercise bout, SIE acutely improves insulin sensitivity above continuous exercise. The higher post-exercise hyperinsulinemia and the inhibition of lipolysis could be behind the marked insulin sensitivity improvement after SIE.