Plasma Fatty Acid Research Articles

Circulating saturated fatty acids and risk of gestational diabetes mellitus: A cross-sectional study and meta-analysis.

BackgroundPrevious studies have analyzed the associations between the circulating saturated fatty acids (SFAs) and gestational diabetes mellitus (GDM), but no consistent conclusions have been reached. The aim of this study was to evaluate whether plasma SFAs were in correlation with GDM risks in our in-house women cross-sectional study and to better define their associations on the clinical evidence available to date by a dose-response meta-analysis.MethodsWe carried out a cross-sectional study of 807 pregnant women in 2018–2019 (Shanghai, China). GDM was defined according to the criteria of the International Association of Diabetes and Pregnancy Study Groups (IADPSG). Gas chromatography was used to determine the plasma fatty acids (FAs) in the 24–28 gestational weeks. The SFAs levels of non-GDM and GDM participants were compared by Mann–Whitney test, and the association between SFAs and GDM was explored by multivariate logistic models. Further, the potential diagnostic value of plasma SFAs was evaluated using the method of receiver operating characteristic (ROC) analysis. For meta-analysis, five databases were systematically searched from inception to March 2022, and we included 25 relevant studies for calculating pooled standard mean differences (SMDs) and 95% CI to describe the differences in SFAs profiles between non-GDM and GDM women. Study-specific, multivariable-adjusted ORs and 95% CI were also pooled using a fixed-effect model or random-effects model according to the heterogeneity to evaluate the associations between circulating SFAs and GDM prevalence.ResultsIn our cross-sectional study, we found plasma proportion of palmitic acid (C16:0) was positively associated (aOR: 1.10 per 1% increase; 95% CI: 1.04, 1.17), while plasma stearic acid (C18:0) (aOR: 0.76 per 1% increase; 95% CI: 0.66, 0.89), arachidic acid (C20:0) (aOR: 0.92 per 0.1% increase; 95% CI: 0.87, 0.97), behenic acid (C22:0) (aOR: 0.94 per 0.1% increase; 95% CI: 0.92, 0.97), and lignoceric acid (C24:0) (aOR: 0.94 per 0.1% increase; 95% CI: 0.92, 0.97) were inversely associated with GDM. The area under the receiver operative characteristic curve increased from 0.7503 (the basic diagnostic model) to 0.8178 (p = 0.002) after adding total very-long-chain SFAs (VLcSFAs). A meta-analysis from 25 studies showed the circulating levels of three individual SFAs of GDM women were different from those of normal pregnant women. The summarized ORs for GDM was 1.593 (95% CI: 1.125, 2.255, p = 0.009), 0.652 (95% CI: 0.472, 0.901, p = 0.010) and 0.613 (95% CI: 0.449, 0.838, p = 0.002), respectively, comparing the highest vs. lowest quantile of the concentrations of C16:0, C22:0, and C24:0.ConclusionOur results, combined with the findings from meta-analysis, showed that women with GDM had a particular circulating SFA profile, characterized by higher levels of palmitic acid, and lower levels of VLcSFAs. Alterations in the chain lengths of blood SFA profile were shown to be associated with the occurrence of GDM.

Elevated stearoyl-CoA desaturase 1 activity is associated with alcohol-associated liver disease.

Chronic binge drinking induces hepatic lipid accumulation, but only certain individuals develop alcohol-associated liver disease (ALD). Specific patterns of lipid accumulation are thought to be associated with ALD, but this has not been comprehensively investigated to date. We analyzed plasma fatty acid levels, quantified by gas chromatography-mass spectrometry, in a sample of patients with alcohol use disorder (AUD). Given that elevation in serum alanine transaminase (ALT) levels are strongly associated with ALD, patients were stratified into two groups based on ALT levels: an ALD group (ALT >40 IU/L) and a non-ALD group (ALT ≤40 IU/L). There was a shift toward greater concentrations of monounsaturated fatty acids in the ALD group compared to the non-ALD group. Stearoyl-CoA desaturase (SCD1) activity in the ALD group was then estimated as the ratio of palmitoleic acid (16:1) to palmitic acid (16:0). SCD1 activity was greater in the ALD than the non-ALD group. A series of linear regression models demonstrated that SCD1 activity mediated the association between binge drinking and ALD. These findings provide initial evidence that SCD1 activity may be associated with ALD. If validated prospectively, elevated SCD1 activity could potentially be used as a biomarker to identify individuals at high risk for developing ALD.

Effect of Flaxseed Supplementation on Milk and Plasma Fatty Acid Composition and Plasma Parameters of Holstein Dairy Cows.

Simple SummaryFew articles have reported the influence of whole and ground flaxseed intake on milk longer chain n-3 polyunsaturated fatty acid (PUFA) and the efficiency of diet α-linolenic acid (ALA) to convert to milk (milk ALA/ALA intake ratio). The objective of this experiment was to explore the effect of whole and ground flaxseed supplementation on the composition of n-3 polyunsaturated fatty acid (PUFA) in milk from dairy cows. This result indicated that whole and ground flaxseed supplementation can increase total n-3 PUFA. Compared with whole flaxseed, ground flaxseed supplementation showed higher content and yield of ALA in milk and milk ALA/ALA intake.The objective of this study was to determine the effect of whole flaxseed and ground flaxseed supplementation on the composition of fatty acids in plasma and milk, particularly the content of omega-3 polyunsaturated fatty acids (n-3 PUFAs). Thirty Holstein dairy cows were randomly assigned to three treatment groups. Cows were fed a total mixed ration without flaxseed (CK), 1500 g of whole flaxseed (WF), and 1500 g of ground flaxseed (GF) supplementation. There were no differences observed in dry matter intake, milk yield, energy-corrected milk, and 4% fat-corrected milk (p > 0.05). Compared with the CK group, the contents of α-linolenic acid (ALA), eicosatrienoic acid, and eicosapentaenoic acid increased in the plasma and milk WF and GF groups, and the content of docosahexaenoic acid and total n-3 PUFA was higher in GF than the other groups (p < 0.001). The ALA yield increased to 232% and 360% in WF and GF, respectively, compared to the CK group. Compared with the WF group, GF supplementation resulted in an increased milk ALA/ALA intake ratio (p < 0.001). Flaxseed supplementation increased the activity of GSH-Px and decreased the concentration of MDA in milk (p < 0.001). Plasma parameters did not differ among the treatments (p > 0.05). This result indicated that compared with the WF group, GF supplementation in the diet showed higher efficiency in increasing the total n-3 PUFA levels and the milk ALA/ALA intake ratio, and decreased the ratio of n-6 PUFAs to n-3 PUFAs in milk.

The association between heightened ADHD symptoms and cytokine and fatty acid concentrations during pregnancy.

ObjectivePrevious research conducted with samples of children suggest that individuals with attention-deficit/hyperactivity disorder (ADHD) have altered fatty acid concentrations and may have increased systemic inflammation. Whether these differences are also apparent in other populations of individuals with heightened ADHD symptoms (e.g., pregnant adults) is unknown. The goal of the current study was to examine whether there are ADHD-associated differences in polyunsaturated fatty acid concentrations or pro-inflammatory cytokine concentrations during pregnancy, a developmental period when fatty acid concentrations and systemic inflammation have implications for the health of both the pregnant person and the developing child. We hypothesized that plasma levels of the ratio of omega-6s to omega-3s (n-6:n-3) and plasma inflammatory cytokine levels would be higher in individuals with heightened ADHD symptoms, consistent with previous findings in children with ADHD.MethodsData (N = 68) came from a prospective study of pregnant community volunteers who were oversampled for ADHD symptoms. During the 3rd trimester, plasma concentrations of fatty acids and the pro-inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were assessed. Dietary intake was examined in the 3rd trimester using three 24-h recalls conducted by trained dietitians and by examining plasma levels of conjugated linoleic acid (n-6) and α-linolenic acid (n-3), essential fatty acids that must come from dietary intake.ResultsThe group with heightened ADHD symptoms had higher n-6:n-3s (β = 0.30, p < 0.01) and higher TNF-α concentrations (β = 0.35, p < 0.001) relative to controls. There were no group differences in dietary variables, as assessed by self-report and via plasma concentrations of essential fatty acids. IL-6 was not reliably associated with ADHD status in this sample.ConclusionPregnant individuals with ADHD, on average, had higher plasma n-6:n-3s and higher TNF-α concentrations relative to controls. A difference was not detected in their dietary intake of fatty acids or other relevant nutrients. Though these null findings are inconclusive, they are consistent with the hypothesis that ADHD-associated differences in plasma fatty acid concentrations are the result of ADHD-associated differences in fatty acid metabolism, rather than simply differences in dietary intake.

The association of dietary intake and plasma fatty acid panel in pancreatic cancer patients: Results from Golestan cohort study.

High mortality rate of pancreatic cancer (PC) as one of the most common cancers worldwide made it a center of attention for recent researches on its pathology, etiology, screening and early diagnosis. In previous researches, association of dietary intake and plasma levels of fatty acids with risk of pancreatic cancer was investigated. In this study we aimed to evaluate the correlation between dietary and plasma fatty acids in case and control groups. From 50,045 adults between 40-75 years old participated in Golestan cohort study, fifty incident cases of PC were diagnosed and 150 controls matched by age, sex and residence place were randomly selected. Dietary intakes and plasma levels of fatty acids was evaluated by validated food-frequency questionnaire (FFQ) and Gas Chromatography - Flame Ionization Detector (GC-FID), respectively. Then, Spearman's correlation was used to measure the correlation between dietary and plasma levels of fatty acids in case and control groups. Among all the fatty acids, there was a significant association between plasma and dietary intake of a few fatty acids including trans fatty acids (TFA), polyunsaturated fatty acids (PUFA), 22:6n-3 and 14:0 only in control group. Only total PUFA intake modified plasma level of some fatty acids in case group. There was no difference between association of desaturase enzymes and fatty acids in case and controls. Since, plasma levels of fatty acids might be influenced by recent diet, we did not find any specific differences between the associations of plasma levels of fatty acids with dietary intake of fats in case and control groups.

Are fatty acids and fatty acid binding proteins novel biomarkers for cryoablation efficiency?

PurposeCryoablation is a recommended, modern and well-tolerated method of treating atrial fibrillation (AF). The study evaluates plasma biomarkers related to AF and the effectiveness of its treatment – cryoablation. Heart- and adipocyte-type fatty acid binding proteins (H-FABP and A-FABP, respectively) as well as fatty acids (FAs) were assessed in patients that underwent cryoballoon ablation (CBA) for AF. Patients and methodsConcentrations of plasma FABPs and FAs were measured in 33 AF patients on admission and 24 ​h after CBA (enzyme-linked immunoassay and gas liquid chromatography, respectively). The control group consisted of 20 volunteers. ResultsWe showed that plasma H-FABP and A-FABP concentrations were significantly higher in the patients with AF than in the control group (1135 ​pg/mL vs 836 ​pg/mL, and 34.29 ​ng/mL vs 15.14 ​ng/mL, respectively; p ​< ​0.05). After CBA, H-FABP plasma concentration increased even further (1574 ​pg/mL vs 1135 ​pg/mL; p ​< ​0.05) and FAs levels decreased concomitantly. AF recurred in 8 patients (24.25%) after 3 months and in 13 patients (39.4%) after 6 months. Initially higher concentration of oleic acid (680.24 ​± ​189.768 vs 567.04 ​± ​70.002; p ​< ​0.05) correlated substantially with lower AF relapse rate in 6 months follow-up. ConclusionsThe patients with AF showed increased concentration of H-FABP, whereas CBA triggered further elevation of H-FABP with a simultaneous decline in the total plasma FAs concentration. H-FABP and A-FABP could not be confirmed as new biomarkers of cryoablation efficiency, but this requires further investigation due to the limitations of the study.

Dietary and Plasma Phospholipid Profiles in Vegans and Omnivores-Results from the RBVD Study.

Over the last few years, the vegan diet has become increasingly popular in Germany. It has been proposed that this diet is generally lower in fat, but less is known about the impact on fatty acid (FA) profiles. Therefore, the cross-sectional “Risks and Benefits of a Vegan Diet” (RBVD) study (n = 72) was used to investigate dietary FA intake as well as plasma phospholipid FA in vegans (n = 36) compared to omnivores (n = 36). Vegans had a significantly lower dietary intake of total fat (median 86 g/day, IQR 64–111) in comparison to omnivores (median 104 g/day, IQR 88–143, p = 0.004). Further, vegans had a lower intake of saturated fatty acids (SFA) (p < 0.0001) and monounsaturated fatty acids (MUFA) (p = 0.001) compared to omnivores. Vegans had a higher intake in total polyunsaturated fatty acids (PUFA), omega-3 and omega-6 PUFA compared to omnivores, but without statistical significance after Bonferroni correction. According to plasma phospholipid profiles, relatively lower proportions of SFA (p < 0.0001), total trans fatty acids (TFA) (p = 0.0004) and omega-3-FA (p < 0.0001), but higher proportions of omega-6-FA (p < 0.0001) were observed in vegans. With the exception of omega-3 PUFA, a vegan diet is associated with a more favorable dietary fat intake and more favorable plasma FA profiles and therefore may reduce cardiovascular risk.

Trophic niche partitioning of five sympatric shark species in the tropical eastern Pacific Ocean revealed by multi-tissue fatty acid analysis

Fatty acid (FA) analysis of consumer tissues has recently shown utility in drawing further inferences about trophic niche dynamics of marine predators such as sharks. In this study, we examined liver, plasma, and muscle FAs in five coexisting pelagic sharks (blue (Prionace glauca), silky (Carcharhinus falciformis), bigeye thresher (Alopias superciliosus), pelagic thresher (Alopias pelagicus), and smooth hammerhead (Sphyrna zygaena)) inhabiting the tropical eastern Pacific Ocean. Results showed complex inter- and intra-individual and tissue variation among the five shark species. Based on multivariate analysis of the muscle FAs, P. glauca and C. falciformis have the largest FA niche widths, indicating diverse feeding habits or habitat isolation, whereas A. pelagicus and S. zygaena occupied a narrower niche width, reflecting increased trophic specialization. High percentages of muscle FA niche overlap indicated strong resource competition between S.zygaena and C. falciformis and a degree of dietary isolation by P. glauca. Interpretations of feeding ecology differed based on the analysis of plasma FAs, which could be attributed to higher dietary FA turnover rates. The liver was deemed unsuitable to examine FA niche metrics based on high and unexplained intra-specific variance in liver FAs as well as the unique lipid metabolism in chondrichthyans. Overall, our multi-tissue approach revealed the magnitude of potential competitive interactions among coexisting tropical shark species. It also expanded our understanding of inter-tissue variability and best practices when using FA analysis to estimate trophic niche metrics of sharks.

Association of placental fatty acid desaturase 2 (FADS2) methylation with maternal fatty acid levels in women with preeclampsia

IntroductionBiosynthesis of long-chain polyunsaturated fatty acids requires sequential activities of desaturases and elongases for conversion of fatty acid precursors to products. The delta-6 desaturase enzyme, encoded by FADS2 gene, is a rate limiting enzyme in this pathway. Alterations in D6D enzyme activity can lead to altered fatty acid profiles. ObjectivesTo examine differences in placental DNA methylation (DNAm) and expression of FADS2 gene in preeclampsia women compared to normal women and their association with maternal variables (plasma fatty acids, desaturase enzyme index, blood pressure), placental weight and birth outcomes. MethodsDNAm and expression of FADS2 gene were examined in placentae of normotensive (n = 100) control and preeclampsia (n = 100) women using pyrosequencing and quantitative real-time PCR respectively. Women with preeclampsia included those delivering at term (n = 43, gestation ≥ 37 weeks; T-PE) or preterm (n = 57, gestation < 37 weeks; PT-PE). A total of 26 CpGs in FADS2 promoter and region around it, were analysed in two PCR reactions (region 1 and 2). ResultsOut of 13 CpGs in region 1, significant hypermethylation was noted at CpG3 in T-PE (p = 0.03) and of 13 CpGs in region 2, CpG2 (p = 0.008), CpG11 (p = 0.04), CpG12 (p = 0.001) were hypomethylated and CpG13 (p = 0.001) was hypermethylated in preeclampsia group, as compared to controls. FADS2 expression was lower in PT-PE as compared to controls (p = 0.04). DNAm at various CpGs in the FADS2 were associated with maternal plasma FADS2 enzyme index and also associated with maternal fatty acid levels. However, we did not observe any association of DNAm with maternal blood pressure, placental weight and birth outcomes. ConclusionsThis study for the first time reports differential methylation of FADS2 and its association with impaired maternal fatty acid metabolism in preeclampsia and provides a mechanistic basis to our earlier observations of altered maternal LCPUFA levels in women with preeclampsia.

Fatty acid metabolism is involved in both retinal physiology and the pathology of retinal vascular diseases

To study the pathophysiological roles of the fatty acid-binding proteins (FABPs) within the retina, we performed; (1) immunolabeling of human retinas, wild type (WT) rat and mouse retinas, rat models for diabetic retinopathy (DR) and retinitis pigmentosa (RP) with anti-FABP3, FABP4, FABP5, FABP7, FABP8 and FABP12, (2) electroretinogram (ERG) measurements of WT and FABP4-deficient (Fabp4-/-) mice, (3) ELISA or gas chromatography measurements of plasma (P-) and vitreous (V-) levels of FABP4 and vascular endothelial growth factor A (VEGFA), and fatty acids (FAs) from patients with retinal vascular disease (RVD) including proliferative DR (PDR, n = 30) and retinal vein occlusion (RVO, n = 18) and non-RVD (n = 18). Within the human retina, diverse expressions of FABP3, FABP4, FABP7 and FABP8 were identified. In contrast, positive immunoreactivities toward only FABP4 and FABP12 were detected in the cases of rat and mouse retinas, and interestingly, the FABP4 labeling patterns for the WT, DR and RP rat retinas were different. The ERG amplitudes of Fabp4-/- mice were enhanced compared with those of WT mice. The concentrations of V-FABP4, V-VEGFA and total FAs were significantly higher in RVD patients than in non-PDR patients (P < 0.05). The V-FAs levels of each were significantly and positively correlated with V-FABP4 and V-VEGFA, although no significant correlation between vitreous (V-) and plasma (P-) FABP4, VEGFA and FAs were detected. The current study reveals that V-FAs appear to have significant roles in both retinal physiology as well as the pathogenesis of RVD with FABP4, which is commonly expressed within the retina in most species.

Effects of HIV Infection in Plasma Free Fatty Acid Profiles among People with Non-Alcoholic Fatty Liver Disease.

Despite its high prevalence, the mechanisms underlying non-alcoholic fatty liver disease (NAFLD) in people living with HIV (PLWH) are still unclear. In this prospective cohort study, we aim to evaluate differences in plasma fatty acid profiles between HIV-infected and HIV-uninfected participants with NAFLD. We included participants diagnosed with NAFLD, both HIV-infected and HIV-uninfected. Fatty acid methyl esters were measured from plasma samples. Ratios ([product]/[substrate]) were used to estimate desaturases and elongases activity. We used linear regression for adjusted analyses. We included 31 PLWH and 22 HIV-uninfected controls. We did not find differences in the sum of different types of FA or in FA with a greater presence of plasma. However, there were significant differences in the distribution of some FA, with higher concentrations of ALA, trans-palmitoleic, and behenic acids, and a lower concentration of lignoceric acid in PLWH. PLWH had lower C24:0/C22:0 and C16:0/C14:0 ratios, which estimates the activity of elongases ELOVL1 and ELOVL6. Both groups had similar fatty acid distribution, despite differences in traditional risk factors. PLWH had a lower proportion of specific ratios that estimate ELOVL1 and ELOVL6 activity, which had been previously described for other inflammatory conditions, such as psoriasis.

Enriched Marine Oil Supplement Increases Specific Plasma Specialized Pro-Resolving Mediators in Adults with Obesity

Specialized pro-resolving mediators (SPMs), synthesized from PUFAs, resolve inflammation and return damaged tissue to homeostasis. Thus, increasing metabolites of the SPM biosynthetic pathway may have potential health benefits for select clinical populations, such as subjects with obesity who display dysregulation of SPM metabolism. However, the concentrations of SPMs and their metabolic intermediates in humans with obesity remains unclear. The primary objective of this study was to determine if a marine oil supplement increased specific metabolites of the SPM biosynthetic pathway in adults with obesity. The second objective was to determine if the supplement changed the relative abundance of key immune cell populations. Finally, given the critical role of antibodies in inflammation, we determined if ex vivo CD19+B-cell antibody production was modified by marine oil intervention. Twenty-three subjects [median age: 56 y; BMI (in kg/m2): 33.1] consumed 2g/d of a marine oil supplement for 28-30 d. The supplement was particularly enriched with 18-hydroxyeicosapentaenoic (HEPE), 14-hydroxydocosahexaenoic acid (14-HDHA), and 17-HDHA. Blood was collected pre- and postsupplementation for plasma mass spectrometry oxylipin and fatty acid analyses, flow cytometry, and B-cell isolation. Paired t-tests and Wilcoxon tests were used for statistical analyses. Relative to preintervention, the supplement increased 6 different HEPEs and HDHAs accompanied by changes in plasma PUFAs. Resolvin E1 and docosapentaenoic acid-derived maresin 1 concentrations were increased 3.5- and 4.7-fold upon intervention, respectively. The supplement did not increase the concentration of D-series resolvins and had no effect on the abundance of immune cells. Ex vivo B-cell IgG but not IgM concentrations were lowered postsupplementation. A marine oil supplement increased select SPMs and their metabolic intermediates in adults with obesity. Additional studies are needed to determine if increased concentrations of specific SPMs control the resolution of inflammation in humans with obesity. This trial was registered at clinicaltrials.gov as NCT04701138.

Potential risks and health benefits of fish in the diet during the childbearing period: Focus on trace elements and n-3 fatty acid content in commonly consumed fish species from the Adriatic Sea

Fish is important staple in the human diet and also a primary source of highly toxic methylmercury exposure. This study evaluates total mercury (THg), total arsenic (TAs) and selenium (Se) levels together with potential health risks and benefits of habitual fish diet in healthy postpartum women in coastal Croatia (n = 100). Self-reported fish intake habits were recorded by a semi-quantitative food frequency questionnaire. Elements were analyzed in maternal hair and blood/serum as well as in most frequently consumed fish specimens and products by inductively coupled plasma mass spectrometry and fatty acids, including eicosapentaenoic plus docosahexaenoic n-3 polyunsaturated fatty acids (EPA plus DHA), were determined in raw Adriatic fish by gas chromatography. The estimated average fish consumption frequency was 1.9 servings per week. Median THg levels above the European regulatory limit were reached only in wild Adriatic gilthead seabream. Maternal THg and TAs levels correlated positively with fish consumption (ρ = 0.262, 0.357 and 0.342, respectively) and serum Se was lower in cigarette smokers (p < 0.05). It was concluded that in women during the childbearing period 2–3 servings per week of commonly consumed fish species originated mostly from the Adriatic Sea provides the desired intake of beneficial micronutrients Se and EPA plus DHA. In sensitive subpopulations with habitual fish rich diet, species with high Hg content should be identified, such as wild Adriatic gilthead seabream recognized in this study for which is recommended that it should be consumed not more than once a week to prevent potential health risks.

Effects of Raw and Pasteurized Camel Milk on Metabolic Responses in Pigs Fed a High-Fat Diet.

Simple SummaryCamel milk (CM) contains insulin-like peptides and is high in vitamin C, vitamin E, and antioxidants. Previous studies in diabetic mice and humans have demonstrated a positive impact of CM consumption on glycemic balance, potentially greater than that observed for the consumption of bovine milk. Thus, CM may be a viable therapeutic treatment for diabetic humans, although the mode of action of these effects are not yet understood. This experiment used a high-fat diet as a monogastric model to examine the effect of CM consumption (raw or pasteurized) on some key blood metabolic markers and examined responses to an in vitro glucose tolerance test. While the results are preliminary given the low number of animals, this experiment suggested that CM can improve glycemic control, potentially via a tighter control of insulin effectiveness and/or uptake.Evidence suggests that camel milk (CM) can have insulin-like actions, although the mode of action is not understood. Using the pig as a monogastric model, this pilot experiment examined the effects of CM consumption on metabolic responses to an in vitro glucose tolerance test (IVGTT). Twenty female Large White × Landrace pigs were individually housed for 6 wks and randomly allocated to one of the following four diets (fed ad libitum; n = 5): control (Con); high fat (HF; ~16% fat); raw CM (the HF diet plus 500 mL CM/ day); or pasteurized CM (PCM). Blood samples were collected on two occasions (weeks 2 and 5). At week 6, the pigs were fitted with an ear vein cannula and the following day an in vitro glucose tolerance test (IVGTT) was conducted (0.3 g/kg BW glucose). Plasma fatty acids and cholesterol concentrations were greater in the pigs fed the HF diet and greatest in those fed CM, while there was no effect of diet on insulin concentrations. The pigs fed CM tended to have a reduced peak insulin (p = 0.058) and an increased glucose nadir (p = 0.009) in response to the IVGTT. These preliminary results tend to support the hypothesis that feeding CM can improve glycemic control in pigs.

FADS Polymorphisms Affect the Clinical and Biochemical Phenotypes of Metabolic Syndrome.

Long-chain polyunsaturated fatty acids (LC-PUFAs) play important roles in human health, from controlling inflammation to lipid and glucose homeostasis. In our previous study, which employed a cluster analysis of a plasma fatty acid (FA) pattern, we identified two clusters of metabolic syndrome (MetS) independent of clinical and biochemical parameters within the whole study group (controls together with metabolic syndrome (MetS) patients). FA desaturase (FADS) genes are the key regulators of LC-PUFA metabolism. The aim of this study was to analyze associations between FADS polymorphisms and clusters of MetS. The study group consisted of 188 controls and 166 patients with MetS. The first cluster contained 71 controls (CON1) and 109 MetS patients (MetS1). The second cluster consisted of 117 controls (CON2) and 57 MetS patients (MetS2). In comparison with MetS2, cluster MetS1 displayed a more adverse risk profile. Cluster CON1 had, in comparison with CON2, higher body weight and increased triacylglycerol levels (p < 0.05). We found that the FADS rs174537 (p < 0.001), rs174570 (p < 0.01), and rs174602 (p < 0.05) polymorphisms along with two inferred haplotypes had statistically significant genotype associations with the splitting of MetS into MetS1 and MetS2. Conversely, we observed no significant differences in the distribution of FADS polymorphisms between MetS and CON subjects, or between CON1 and CON2. These associations between FADS polymorphisms and two clusters of MetS (differing in waist circumference, HOMA-IR, lipolysis, and oxidative stress) implicate the important influence of genetic factors on the phenotypic manifestation of MetS.

Thermogenesis is supported by high rates of circulatory fatty acid and triglyceride delivery in highland deer mice.

Highland native deer mice (Peromyscus maniculatus) have greater rates of lipid oxidation during maximal cold challenge in hypoxia (hypoxic cold-induced V̇O2,max) compared with their lowland conspecifics. Lipid oxidation is also increased in deer mice acclimated to simulated high altitude (cold hypoxia), regardless of altitude ancestry. The underlying lipid metabolic pathway traits responsible for sustaining maximal thermogenic demand in deer mice is currently unknown. The objective of this study was to characterize key steps in the lipid oxidation pathway in highland and lowland deer mice acclimated to control (23°C, 21 kPa O2) or cold hypoxic (5°C, 12 kPa O2) conditions. We hypothesized that capacities for lipid delivery and tissue uptake will be greater in highlanders and further increase with cold hypoxia acclimation. With the transition from rest to hypoxic cold-induced V̇O2,max, both highland and lowland deer mice showed increased plasma glycerol concentrations and fatty acid availability. Interestingly, acclimation to cold hypoxia led to increased plasma triglyceride concentrations at cold-induced V̇O2,max, but only in highlanders. Highlanders also had significantly greater delivery rates of circulatory free fatty acids and triglycerides due to higher plasma flow rates at cold-induced V̇O2,max. We found no population or acclimation differences in fatty acid translocase (FAT/CD36) abundance in the gastrocnemius or brown adipose tissue, suggesting that fatty acid uptake across membranes is not limiting during thermogenesis. Our data indicate that circulatory lipid delivery plays a major role in supporting the high thermogenic rates observed in highland versus lowland deer mice.

The FADS1 genotypes modify the effect of linoleic acid-enriched diet on adipose tissue inflammation via pro-inflammatory eicosanoid metabolism

PurposeFatty acid desaturase (FADS) variants associate with fatty acid (FA) and adipose tissue (AT) metabolism and inflammation. Thus, the role of FADS1 variants in the regulation of dietary linoleic acid (LA)-induced effects on AT inflammation was investigated.MethodsSubjects homozygotes for the TT and CC genotypes of the FADS1-rs174550 (TT, n = 25 and CC, n = 28) or -rs174547 (TT, n = 42 and CC, n = 28), were either recruited from the METabolic Syndrome In Men cohort to participate in an intervention with LA-enriched diet (FADSDIET) or from the Kuopio Obesity Surgery (KOBS) study. GC and LC–MS for plasma FA proportions and eicosanoid concentrations and AT gene expression for AT inflammatory score (AT-InSc) was determined.ResultsWe observed a diet-genotype interaction between LA-enriched diet and AT-InSc in the FADSDIET. In the KOBS study, interleukin (IL)1 beta mRNA expression in AT was increased in subjects with the TT genotype and highest LA proportion. In the FADSDIET, n-6/LA proportions correlated positively with AT-InSc in those with the TT genotype but not with the CC genotype after LA-enriched diet. Specifically, LA- and AA-derived pro-inflammatory eicosanoids related to CYP450/sEH-pathways correlated positively with AT-InSc in those with the TT genotype, whereas in those with the CC genotype, the negative correlations between pro-inflammatory eicosanoids and AT-InSc related to COX/LOX-pathways.ConclusionsLA-enriched diet increases inflammatory AT gene expression in subjects with the TT genotype, while CC genotype could play a protective role against LA-induced AT inflammation. Overall, the FADS1 variant could modify the dietary LA-induced effects on AT inflammation through the differential biosynthesis of AA-derived eicosanoids.

Determinants of blood acylcarnitine concentrations in healthy individuals of the European Prospective Investigation into Cancer and Nutrition

SummaryBackground & aimsCirculating levels of acylcarnitines (ACs) have been associated with the risk of various diseases such as cancer and type 2 diabetes. Diet and lifestyle factors have been shown to influence AC concentrations but a better understanding of their biological, lifestyle and metabolic determinants is needed.MethodsCirculating ACs were measured in blood by targeted (15 ACs) and untargeted metabolomics (50 ACs) in 7770 and 395 healthy participants of the European Prospective Investigation into Cancer and Nutrition (EPIC), respectively. Associations with biological and lifestyle characteristics, dietary patterns, self-reported intake of individual foods, estimated intake of carnitine and fatty acids, and fatty acids in plasma phospholipid fraction and amino acids in blood were assessed.ResultsAge, sex and fasting status were associated with the largest proportion of AC variability (partial-r up to 0.19, 0.18 and 0.16, respectively). Some AC species of medium or long-chain fatty acid moiety were associated with the corresponding fatty acids in plasma (partial-r = 0.24) or with intake of specific foods such as dairy foods containing the same fatty acid. ACs of short-chain fatty acid moiety (propionylcarnitine and valerylcarnitine) were moderately associated with concentrations of branched-chain amino acids (partial-r = 0.5). Intake of most other foods and of carnitine showed little association with AC levels.ConclusionsOur results show that determinants of ACs in blood vary according to their fatty acid moiety, and that their concentrations are related to age, sex, diet, and fasting status. Knowledge on their potential determinants may help interpret associations of ACs with disease risk and inform on potential dietary and lifestyle factors that might be modified for disease prevention.

Activated autophagy-lysosomal pathway in dairy cows with hyperketonemia is associated with lipolysis of adipose tissues

Activated autophagy-lysosomal pathway (ALP) can degrade virtually all kinds of cellular components, including intracellular lipid droplets, especially during catabolic conditions. Sustained lipolysis and increased plasma fatty acids concentrations are characteristic of dairy cows with hyperketonemia. However, the status of ALP in adipose tissue during this physiological condition is not well known. The present study aimed to ascertain whether lipolysis is associated with activation of ALP in adipose tissues of dairy cows with hyperketonemia and in calf adipocytes. In vivo, blood and subcutaneous adipose tissue (SAT) biopsies were collected from nonhyperketonemic (nonHYK) cows [blood β-hydroxybutyrate (BHB) concentration <1.2 mM, n = 10] and hyperketonemic (HYK) cows (blood BHB concentration 1.2-3.0 mM, n = 10) with similar days in milk (range: 3-9) and parity (range: 2-4). In vitro, calf adipocytes isolated from 5 healthy Holstein calves (1 d old, female, 30-40 kg) were differentiated and used for (1) treatment with lipolysis inducer isoproterenol (ISO, 10 µM, 3 h) or mammalian target of rapamycin inhibitor Torin1 (250 nM, 3 h), and (2) pretreatment with or without the ALP inhibitor leupeptin (10 μg/mL, 4 h) followed by ISO (10 µM, 3 h) treatment. Compared with nonHYK cows, serum concentration of free fatty acids was greater and serum glucose concentration, DMI, and milk yield were lower in HYK cows. In SAT of HYK cows, ratio of phosphorylated hormone-sensitive lipase to hormone-sensitive lipase, and protein abundance of adipose triacylglycerol lipase were greater, but protein abundance of perilipin 1 (PLIN1) and cell death-inducing DNA fragmentation factor-α-like effector c (CIDEC) was lower. In addition, mRNA abundance of autophagy-related 5 (ATG5), autophagy-related 7 (ATG7), and microtubule-associated protein 1 light chain 3 beta (MAP1LC3B), protein abundance of lysosome-associated membrane protein 1, and cathepsin D, and activity of β-N-acetylglucosaminidase were greater, whereas protein abundance of sequestosome-1 (p62) was lower in SAT of HYK cows. In calf adipocytes, treatment with ISO or Torin1 decreased protein abundance of PLIN1, and CIDEC, and triacylglycerol content in calf adipocytes, but increased glycerol content in the supernatant of calf adipocytes. Moreover, the mRNA abundance of ATG5, ATG7, and MAP1LC3B was upregulated, the protein abundance of lysosome-associated membrane protein 1, cathepsin D, and activity of β-N-acetylglucosaminidase were increased, whereas the protein abundance of p62 was decreased in calf adipocytes treated with ISO or Torin1 compared with control group. Compared with treatment with ISO alone, the protein abundance of p62, PLIN1, and CIDEC, and triacylglycerol content in calf adipocytes were higher, but the glycerol content in the supernatant of calf adipocytes was lower in ISO and leupeptin co-treated group. Overall, these data indicated that activated ALP is associated with increased lipolysis in adipose tissues of dairy cows with hyperketonemia and in calf adipocytes.

Changes in plasma total saturated fatty acids and palmitic acid are related to pro-inflammatory molecule IL-6 concentrations after nutritional intervention for one year.

Systemic inflammation is associated with an increased risk of non-communicable diseases, such as cardiovascular diseases and diabetes. Circulating fatty acids (FA) are known to be related to these conditions, possibly through their role in inflammation, although different types of FAs can have opposite effects on inflammatory mediators. The aim of the present study was to analyze the association of plasma FAs with inflammatory biomarkers in a PREDIMED trial subsample after one year of intervention. In a one-year longitudinal study of 91 participants of the PREDIMED trial (Barcelona-Clinic center), plasma FAs and inflammatory biomarkers were analyzed using gas chromatography and ELISA, respectively. In baseline plasma, a multivariable-adjusted ordinary least squares regression model showed that n-3 polyunsaturated FAs concentrations were inversely associated with concentrations of soluble intercellular adhesion molecule-1 (sICAM-1) and E-selectin, whereas the level of the most abundant saturated FA, palmitic acid, was directly associated with concentrations of interleukin-6 (IL-6) (β=0.48pg/mL, 95% CI: 0.03, 0.93 per 1-SD increase, p-value = 0.037). After one year of nutritional intervention, changes of plasma diet-derived total saturated FAs and palmitic acid were directly associated with changes in IL-6 (β=0.59pg/mL [95% CI: 0.28, 0.89] per 1-SD, p-value = 0.001; β=0.64pg/mL, 95% CI: 0.31, 0.98, p-value = 0.001), respectively, after correction for multiple testing. Our findings suggest that saturated FAs of dietary origin, especially palmitic acid, are directly involved in the increase of IL-6 in plasma.