Renal tubule-specific Atgl deletion links kidney lipid metabolism to glucagon-like peptide 1 and insulin secretion independent of renal inflammation or lipotoxicity.

OBJECTIVE: Lipotoxic injury from renal lipid accumulation in obesity and type 2 diabetes (T2D) is implicated in associated kidney damage. However, models examining effects of renal ectopic lipid accumulation independent of obesity or T2D are lacking. We generated renal tubule-specific adipose triglyceride lipase knockout (RT-SAKO) mice to determine if this targeted triacylglycerol (TAG) over-storage affects glycemic control and kidney health. METHODS: Male and female RT-SAKO mice and their control littermates were tested for changes in glycemic control at 10-12 and 16-18 weeks of age. Markers of kidney health and blood lipid and hormone concentrations were analyzed. Kidney and blood lysophosphatidic acid (LPA) levels were measured, and a role for LPA in mediating impaired glycemic control was evaluated using the LPA receptor 1/3 inhibitor Ki-16425. RESULTS: All groups remained insulin sensitive, but 16- to 18-week-old male RT-SAKO mice became glucose intolerant, without developing kidney inflammation or fibrosis. Rather, these mice displayed lower circulating insulin and glucagon-like peptide 1 (GLP-1) levels. Impaired first-phase glucose-stimulated insulin secretion was detected and restored by Exendin-4. Kidney and blood LPA levels were elevated in older male but not female RT-SAKO mice, associated with increased kidney diacylglycerol kinase epsilon. Inhibition of LPA-mediated signaling restored serum GLP-1 levels, first-phase insulin secretion, and glucose tolerance. CONCLUSIONS: TAG over-storage alone is insufficient to cause renal tubule lipotoxicity. This work is the first to show that endogenously derived LPA modulates GLP-1 levels in vivo, demonstrating a new mechanism of kidney-gut-pancreas crosstalk to regulate insulin secretion and glucose homeostasis.

Effects of Atorvastatin and Rosuvastatin on Blood Lipids in Quaker Parrots (Myiopsitta monachus).

Statin drugs are the most effective class of hypolipidemic and antiatherosclerotic drugs, with atorvastatin and rosuvastatin being the most effective. While the use of statins would be a tremendous asset in the treatment of dyslipidemia and lipid-accumulation disorders in birds, there are only limited data available regarding their use and effectiveness in psittacine species. Two consecutive randomized crossover trials on Quaker parrots (Myiopsitta monachus) were performed to study the effect of atorvastatin and rosuvastatin. Ten birds were used in an initial balanced crossover experiment with 5 oral treatments (control; atorvastatin 10 mg/kg q12h and q24h; rosuvastatin 10 mg/kg q12h and q24h) for 2 weeks each. Plasma lipidomics and lipoprotein profiling were performed after each treatment. Twelve birds were used in a second experiment consisting of 2 parallel crossover studies, each with 6 birds either fed their regular diet or a 0.3% cholesterol diet. In the 2 parallel crossover studies, the treatment group was administered atorvastatin 20 mg/kg orally q12h and the control group a placebo suspension orally q12h. Plasma lipidomics, lipoprotein profiles, and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity were subsequently measured. Results were analyzed with serial linear mixed models and trends were assessed graphically. No statistically significant effect of any statin treatment was detected on plasma lipids, lipoproteins, creatinine kinase, or HMG-CoA reductase activity. In the first trial, all the rosuvastatin treatments led to some nonsignificant decreases in several triacylglycerol species, while in the second trial this was only observed in the birds on atorvastatin 20 mg/kg q12h being fed their regular diet. Quaker parrots may require much higher doses of statin drugs to show significant and clinically useful lipid-lowering effects.

Phenotypic Characterization of Female Carrier Mice Heterozygous for Tafazzin Deletion.

Barth syndrome (BTHS) is caused by mutations in tafazzin resulting in deficits in cardiolipin remodeling that alter major metabolic processes. The tafazzin gene is encoded on the X chromosome, and therefore BTHS primarily affects males. Female carriers are typically considered asymptomatic, but age-related changes have been reported in female carriers of other X-linked disorders. Therefore, we examined the phenotype of female mice heterozygous for deletion of the tafazzin gene (Taz-HET) at 3 and 12 months of age. Food intakes, body masses, lean tissue and adipose depot weights, daily activity levels, metabolic measures, and exercise capacity were assessed. Age-related changes in mice resulted in small but significant genotype-specific differences in Taz-HET mice compared with their female Wt littermates. By 12 months, Taz-HET mice weighed less than Wt controls and had smaller gonadal, retroperitoneal, and brown adipose depots and liver and brain masses, despite similar food consumption. Daily movement, respiratory exchange ratio, and total energy expenditure did not vary significantly between the age-matched genotypes. Taz-HET mice displayed improved glucose tolerance and insulin sensitivity at 12 months compared with their Wt littermates but had evidence of slightly reduced exercise capacity. Tafazzin mRNA levels were significantly reduced in the cardiac muscle of 12-month-old Taz-HET mice, which was associated with minor but significant alterations in the heart cardiolipin profile. This work is the first to report the characterization of a model of female carriers of heterozygous tafazzin deficiency and suggests that additional study, particularly with advancing age, is warranted.

Changes in polyunsaturated fatty acids during treatment of malnourished children may be insufficient to reach required essential fatty acid levels - A randomised controlled trial.

BACKGROUND & AIMS: Severe acute malnutrition (SAM) is a global concern. Studies on the impact of ready-to-use therapeutic foods (RUTFs) on polyunsaturated fatty acids (PUFA) are almost non-existent. The aim was to investigate the change in whole-blood PUFA and nutrition and health markers among Cambodian children with SAM after treatment with RUTFs. METHODS: The trial was an 8-week randomised clinical trial of the effectiveness of locally produced fish-based RUTF (L-RUTF) vs standard milk-based RUFT (S-RUTF). Whole-blood fatty acids were analysed using dried blood spots. Nutrition and health markers were assessed using anthropometric assessment and blood samples for markers of inflammation. The trial was conducted at the National Pediatric Hospital, Phnom Penh, Cambodia, with one hundred and twenty-one 6-59-month-old children in treatment for SAM. RESULTS: L-RUTF had a higher content of n-3 PUFA and a higher content of arachidonic acid (AA) and docosahexaenoic acid (DHA), while S-RUTF had the highest content of n-6 PUFA. At baseline, the children presented with a Mead acid level in whole-blood of around 0.08% of total fatty acids (FA%) and an omega-3 index of ∼0.91 ± 0.44. After eight weeks of S-RUTF treatment, linoleic acid (LA), AA, n-6/n-3 PUFA ratio, and Mead acid levels were increased. The L-RUTF intervention did not change the whole-blood PUFAs from baseline. At discharge, the children in the L-RUTF group had a lower n-6/n-3 PUFA ratio than the children in the S-RUTF group, driven by a lower alpha-linolenic acid (ALA) (0.20 vs 0.27 FA%, p = 0.004) and lower LA (15.77 vs 14.21 FA%, p = 0.018) with no significant differences in AA or DHA levels. Weight-for-height z-score at discharge was negatively associated with total PUFA (ß -1.4 FA%, 95%CI. -2.7; -0.1), n-6 LCPUFA (ß -1.3 FA%, 95%CI. -1.3; -0.3), and AA (ß -0.6 FA%, 95%CI. -1.0; -0.2). Age-adjusted height was negatively associated with the Mead acid:AA ratio (ß -1.2 FA%, 95%CI. -2.2; -0.2). No significant change was seen in inflammation markers within groups or between groups during treatment, and n-3 and n-6 PUFAs were not associated with markers of inflammation or haemoglobin status at discharge. CONCLUSION: The trial found that whole-blood markers of PUFA status were low in children at admission and discharge from SAM treatment, indicating that the currently recommended composition of RUTFs are not able to correct their compromised essential fatty acid status. The higher content of DHA and AA in L-RUTF did not give rise to any improvement in PUFA status. No changes in health markers or associations between PUFA and health markers were found. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02907424.

Mercury bioaccessiblity in freshwater fish species from northern Canada.

Indigenous communities in northern Canada rely on locally harvested traditional foods, including fish, which provides them with nutritional, cultural, and social benefits. However, mercury exposure from fish consumption can pose a health risk for populations that consume large amounts of fish with elevated mercury concentrations. The bioaccessiblity of mercury in the tissue of northern Canadian freshwater fish is not yet known. To address this, samples from five commonly consumed freshwater fish species (Lake Trout, Northern Pike, Walleye, Lake Whitefish, and Burbot) caught from lakes in the Northwest Territories and Yukon, Canada were examined. Total mercury concentrations, fatty acid composition, and total mercury bioaccessibility differed significantly among fish species and lakes. Mean total mercury bioaccessibility using an in vitro gastrointestinal model ranged between 56 % and 96 % in muscle tissue across fish species and waterbodies examined and was 39 % in liver tissue from Burbot. Mean total mercury bioaccessibility was much lower (range: 38 % to 42 %) for a subset of samples run through only the gastric phase of the digestion model. Total mercury bioaccessibility was significantly lower (on average 40 % lower) in a subset of samples that were pan-fried in water. Thus, although cooking increased total mercury concentrations in pan-fried fish samples (likely due to moisture loss), bioaccessible concentrations of total mercury were lower (on average 32 % lower). Results from this study contribute to addressing a large knowledge gap in the literature regarding bioaccessibility of total mercury in northern freshwater fish species. To the best of our knowledge, this is the first study to examine mercury bioaccessibility in raw and cooked liver samples from freshwater fish. It also adds to the growing literature indicating that mercury bioaccessibility varies among fish species, locations, and cooking/preparation methods.

The effect of traditional diet on glucose homoeostasis in carriers and non-carriers of a common TBC1D4 variant in Greenlandic Inuit: a randomised crossover study.

Consumption of traditional foods is decreasing amid a lifestyle transition in Greenland as incidence of type 2 diabetes (T2D) increases. In homozygous carriers of a TBC1D4 variant, conferring postprandial insulin resistance, the risk of T2D is markedly higher. We investigated the effects of traditional marine diets on glucose homoeostasis and cardio-metabolic health in Greenlandic Inuit carriers and non-carriers of the variant in a randomised crossover study consisting of two 4-week dietary interventions: Traditional (marine-based, low-carbohydrate) and Western (high in imported meats and carbohydrates). Oral glucose tolerance test (OGTT, 2-h), 14-d continuous glucose and cardio-metabolic markers were assessed to investigate the effect of diet and genotype. Compared with the Western diet, the Traditional diet reduced mean and maximum daily blood glucose by 0·17 mmol/l (95 % CI 0·05, 0·29; P = 0·006) and 0·26 mmol/l (95 % CI 0·06, 0·46; P = 0·010), respectively, with dose-dependency. Furthermore, it gave rise to a weight loss of 0·5 kg (95 % CI; 0·09, 0·90; P = 0·016) relative to the Western diet and 4 % (95 % CI 1, 9; P = 0·018) lower LDL:HDL-cholesterol, which after adjustment for weight loss appeared to be driven by HDL elevation (0·09 mmol/l (0·03, 0·15), P = 0·006). A diet-gene interaction was indicated on insulin sensitivity in the OGTT (p = 0·093), which reflected a non-significant increase of 1·4 (-0·6, 3·5) mmol/l in carrier 2-h glucose. A Traditional diet marginally improved daily glycaemic control and plasma lipid profile compared with a Westernised diet in Greenlandic Inuit. Possible adverse effects on glucose tolerance in carriers of the TBC1D4 variant warrant further studies.

Sex differences in hippocampal-dependent memory and the hippocampal lipidome in adolescent rats raised on diets with or without DHA.

Recent studies suggest the effects of DHA supplementation on human memory may differ between females and males during infancy, adolescence, and early adulthood, but the underlying mechanisms are not clear. As a result, this study sought to examine the spatial memory and brain lipidomic profiles in female and male adolescent rats with or without a DHA-enriched diet that began perinatally with the supplementation of dams. Spatial learning and memory were examined in adolescent rats using the Morris Water Maze beginning at 6 weeks of age and animals were sacrificed at 7 weeks of age to permit isolation of brain tissue and blood samples. Behavioral testing showed that there was a significant diet x sex interaction for two key measures of spatial memory (distance to zone and time spent in the correct quadrant during the probe test), with female rats benefiting the most from DHA supplementation. Lipidomic analyses suggest levels of arachidonic acid (ARA) and n-6 docosapentaenoic acid (DPA) containing phospholipid species were lower in the hippocampus of DHA supplemented compared with control animals, and principal component analyses revealed a potential dietary treatment effect for hippocampal PUFA. Females fed DHA had slightly more PE P-18:0_22:6 and maintained levels of PE 18:0_20:4 in the hippocampus in contrast with males fed DHA. Understanding how DHA supplementation during the perinatal and adolescent periods changes cognitive function in a sex-specific manner has important implications for determining the dietary requirements of DHA. This study adds to previous work highlighting the importance of DHA for spatial memory and provides evidence that further research needs to consider how DHA supplementation can cause sex-specific changes.

Comparison of blood leptin and vitamin E and blood and adipose fatty acid compositions in wild and captive populations of critically endangered Vancouver Island marmots (Marmota vancouverensis).

Vancouver Island marmots (Marmota vancouverensis) (VIMs) are a critically endangered species of fat-storing hibernators, endemic to Vancouver Island, British Columbia, Canada. In addition to in-situ conservation efforts, a captive breeding program has been ongoing since 1997. The captive diet is mostly pellet-based and rich in n-6 polyunsaturated fatty acids (PUFAs). In captivity, overall length of hibernation is shortened, and marmots have higher adipose tissue reserves compared to their wild-born counterparts, which may be a risk factor for cardiovascular disease, the leading cause of mortality in captive marmots. To investigate differences in lipid metabolism between wild and captive populations of VIMs, blood vitamin E, fatty acid (FA) profiles and leptin, and white adipose tissue (WAT) FA profiles were compared during the active season (May to September 2019). Gas chromatography, high-performance liquid chromatography, and multiplex kits were used to obtain FA profiles, α-tocopherol, and leptin values, respectively. In both plasma and WAT, the concentration of the sum of all FA in the total lipids was significantly increased in captive VIMs. The n-6/n-3 ratio, saturated FAs, and n-6 PUFAS were higher in captive marmots, whereas n-3 PUFAs and the HUFA score were higher in wild marmots. Serum concentrations of α-tocopherol were greater by an average of 45% in captive marmots, whereas leptin concentrations did not differ. Results from this study may be applied to improve the diet and implement weight management to possibly enhance the quality of hibernation and decrease the risk of cardiovascular and metabolic diseases of captive VIMs.

N-oleoylethanolamide treatment of lymphoblasts deficient in Tafazzin improves cell growth and mitochondrial morphology and dynamics.

Barth syndrome (BTHS) is caused by mutations in the TAZ gene encoding the cardiolipin remodeling enzyme, Tafazzin. The study objective was to quantitatively examine growth characteristics and mitochondrial morphology of transformed lymphoblast cell lines derived from five patients with BTHS relative to five healthy controls, as well as the therapeutic potential of oleoylethanolamide (OEA) and linoleoylethanolamide (LEA). These bioactive lipids both activate PPARα, which may be therapeutic. BTHS lymphoblasts grew more slowly than controls, suggesting lymphopenia merits clinical investigation. Treatment of BTHS lymphoblasts with OEA, but not LEA, significantly restored mitochondrial membrane potential, as well as colony growth in all BTHS lymphoblast lines, although a full growth rescue was not achieved. Quantification analysis of electron micrographs from three BTHS and healthy lymphoblast donors indicated similar numbers of mitochondria per cell, but lower average cristae length per mitochondrion, and higher mitochondrial density. Additionally, BTHS lymphoblasts had larger mitochondria, and a higher percentage of abnormally large mitochondria (> 1 µm2) than healthy controls. Notably, OEA treatment significantly restored mitochondrial size, without affecting density or cristae lengths. Cardiolipin total content, relative linoleic acid content and monolysocardiolipin:cardiolipin ratios were not improved by OEA, indicating that effects on growth, and mitochondrial morphology and function, occurred without resolving this deficit. However, immunoblotting showed higher levels of OPA1, a biomarker for mitochondrial fusion, in BTHS lymphoblasts, which was attenuated by OEA treatment, implicating altered mitochondrial dynamics in the pathology and treatment of BTHS.

PLAAT1 Exhibits Phosphatidylcholine:Monolysocardiolipin Transacylase Activity.

Tissue-specific cardiolipin fatty acyl profiles are achieved by remodeling of de novo synthesized cardiolipin, and four remodeling enzymes have thus far been identified. We studied the enzyme phospholipase A and acyltransferase 1 (PLAAT1), and we report the discovery that it has phosphatidylcholine (PC):monolysocardiolipin (MLCL) transacylase activity. Subcellular localization was analyzed by differential centrifugation and immunoblotting. Total levels of major phospholipids, and the fatty acyl profile of cardiolipin, were analyzed in HEK293 cells expressing murine PLAAT1 using gas chromatography. Apparent enzyme kinetics of affinity-purified PLAAT1 were calculated using radiochemical enzyme assays. This enzyme was found to localize predominantly to the endoplasmic reticulum (ER) but was detected at low levels in the mitochondria-associated ER matrix. Cells expressing PLAAT1 had higher levels of total cardiolipin, but not other phospholipids, and it was primarily enriched in the saturated fatty acids myristate, palmitate, and stearate, with quantitatively smaller increases in the n-3 polyunsaturated fatty acids linolenate, eicosatrienoate, and eicosapentanoate and the monounsaturated fatty acid erucate. Affinity-purified PLAAT1 did not catalyze the transacylation of MLCL using 1-palmitoyl-2-[14C]-linoleoyl-PC as an acyl donor. However, PLAAT1 had an apparent Vmax of 1.61 µmol/min/mg protein and Km of 126 µM using [9,10-3H]-distearoyl-PC as an acyl donor, and 0.61 µmol/min/mg protein and Km of 16 µM using [9,10-3H]-dioleoyl-PC. PLAAT1 is therefore a novel PC:MLCL transacylase.

Effects of a 0.3% cholesterol diet and a 20% fat diet on plasma lipids and lipoproteins in Quaker parrots (Myiopsitta monachus).

BACKGROUND: Lipid disorders are common in captive psittacine birds, but associated changes in blood lipids and lipoproteins have not been well characterized. The Quaker parrot is prone to dyslipidemia and has been extensively used as an experimental model. OBJECTIVES: We aimed to study the effects of a 0.3% cholesterol diet and a 20% fat diet on plasma lipids and lipoproteins in Quaker parrots. METHODS: Two crossover studies were performed with each diet. During each study, 12 parrots were divided into two groups fed the treatment or control diet for 2 weeks. After a 2-month wash-out period, the groups were reversed. At the end of each period, plasma lipidomics and lipoprotein profiling were performed. Data were analyzed by univariate tests adjusted for false discovery rates, volcano plots, and enrichment analyses. RESULTS: The cholesterol diet induced changes in many plasma lipids and lipoproteins. Total cholesterol and cholesteryl esters were significantly and markedly elevated. Ceramides were the second subclass of lipids that were elevated. Several glycerophosphocholines, sphingomyelins, and one diacylglycerol were also significantly elevated, albeit to a lesser magnitude. All lipoproteins were elevated, with the greatest increase seen in non-HDL. The fat diet mainly resulted in a decrease in plasma glycerolipids and an increase in acylcarnitines. Lipoprotein plasma levels remained unchanged. CONCLUSIONS: Quaker parrots fed a 0.3% cholesterol diet showed profound and complex dyslipidemic changes that could be used to further study lipid disorders and their management in psittacine birds. A 20% fat diet higher in n-6 polyunsaturated fatty acids did not lead to dyslipidemia.

Fish oil supplementation may improve attention, working memory and attention-deficit/hyperactivity disorder symptoms in adults with autism spectrum disorder: a randomised crossover trial.

Marine n-3 fatty acids (n-3LCPUFA) have shown neurocognitive benefits in children with attention-deficit/hyperactivity disorder (ADHD), but few trials have examined effects in adults with autism spectrum disorder (ASD). We explored, if n-3LCPUFA affect cognitive functions in adults with ASD, and if effects are modified by comorbid ADHD. In a 2 × 4 week crossover study, twenty-six participants were randomised to sequence of supplementation with fish oil (FO, 5·2 g/d n-3PUFA) and safflower oil (SO). At baseline and after each period, we measured primary outcomes: attention (d2-test) and spatial working memory (Corsi test) and secondary outcomes: flexibility (Stroop word-colour test), ADHD symptoms (Conners scales), executive functions (Behavioural Inventory of Executive Function) and social behaviour (Social Responsiveness Scale). The dropout rate was 15 %. Compliance was 94 % and correlated with whole-blood n-3LCPUFA. Corsi scores improved by ∼0·3 × sd (P = 0·032) after FO v. SO, and the odds for d2 errors were 30 % lower (P = 0·016), which was supported by improved Conners scores of attention (P = 0·023). Improvement in Conners ADHD symptom score was limited to participants with ADHD (-3·5(-6·0; -1·0), n 10 v. -0·2(-2·5;2·2), n 11 without ADHD, Pinteraction = 0·096), who also improved their behavioural regulation index by 0·3 × sd after FO (Pinteraction = 0·016). Participants without ADHD gained most in d2 test performance (OR = 0·4(0·2;0·7) v. 0·9(0·6;1·3) in those with ADHD, Pinteraction = 0·002), but their executive function score was exacerbated after FO (5·9(0·0,11·8), Pinteraction = 0·039). Our results did not show any effects on ASD symptoms, but suggest that FO may improve attention and working memory in adults with ASD and ameliorate ADHD symptoms in those with comorbid ADHD.

Macrolipidomic Profiling of Vegetable Oils: The Analysis of Sunflower Oils with Different Oleic Acid Content.

Conventional breeding techniques and genetic modifications have made it possible to alter the composition of vegetable oils. In recent years, the field of lipidomics has rapidly evolved due to technological developments in mass spectrometry. "Macrolipidomics" is an approach dedicated to detailed characterization of the most abundant lipids of a sample and has the potential to be useful for the profiling of commercial seed oils. Seed oils are composed largely of triacylglycerols (TAG) with various fatty acyls that can result in a number of isobaric and isomeric TAG species in each sample. Comprehensive methods for fatty acyl TAG characterization are still scarce. In this chapter, we describe the steps required to process and analyze different sunflower oils with altered oleic acid content to generate quantitative data for discrete fatty acyl species of TAG molecules. We utilized a dual ultra-high-performance liquid chromatography (UHPLC) serial coupling setup and untargeted tandem mass spectrometry (MS/MS) to quantitate 23 common TAG species in three sunflower oils containing 40% (low), 60% (mid), and 85% (high) oleic acid by weight.

Characterization of a novel FADS2 transcript variant: implications for D6D activity regulation in cells.

Delta-6-desaturase (D6D) activity is deficient in MCF-7 and other cancer cell lines, but it is not explained by FADS2 gene mutations. This deficient activity was not ameliorated by induction of the FADS2 gene; therefore, we hypothesized that some of the induced FADS2 transcript variants (tv) may play a negative regulatory role. FADS2_tv1 is the reference FADS2 tv, coding for full-length D6D isoform 1 (D6D-iso1), and alternative transcriptional start sites result in FADS2_tv2 and FADS2_tv3 variants encoding D6D-iso2 and D6D-iso3 isoforms, respectively, which lack the catalytically critical N-terminal domain. In MCF-7 cells, FADS2_tv2 and FADS2_tv3 were expressed at significantly higher levels than FADS2_tv1. Overexpression of FADS2_tv2 in HEK293 cells confirmed that D6D-iso2 is non-functional, and co-transfection demonstrated a dominant-negative role for D6D-iso2 in D6D-iso1 activity regulation. FADS2_tv2 was expressed at higher levels than FADS2_tv1 in HeLa, MDA-MB-435, MCF-10 A, and HT-29 cells, but at lower levels in A549, MDA-MB-231, and LNCaP cells. Overexpression studies indicated roles for FADS2 variants in proliferation and apoptosis regulation, which were also cell-line specific. Increased FADS2_tv2 expression provides a new mechanism to help explain deficient D6D activity in MCF-7 and other cancer cell lines, but it is not a hallmark of malignant cells.

Evidence of multiple hepatic mechanisms to mobilize docosahexaenoic acid into dam plasma during pregnancy in chow-fed sprague dawley rats.

Fetal brain growth requires considerable amounts of docosahexaenoic acid (DHA) during late pregnancy that is associated with increased maternal/dam plasma levels of PC 16:0_22:6 (palmitoyl docosahexaenoyl phosphatidylcholine). While biosynthesis of DHA during pregnancy is upregulated, the mechanisms responsible for the incorporation of dam DHA into PC 16:0_22:6 are not understood. The present study used a discovery approach combining untargeted lipidomics of plasma and liver (n = 3/group) with semi-targeted qPCR of hepatic gene products (n = 6/group) to identify metabolic pathways related to DHA metabolism, with a hypothesis that an upregulated acyltransferase involved in PC remodeling would be identified. Sprague Dawley rats were fed a commercial rodent chow throughout the study and samples were collected before pregnancy (baseline), at 15 and 20 days of pregnancy, and 7 days postpartum. Plasma and hepatic PC 16:0_22:6 was significantly increased (by 79% and 194%, respectively) at day 20 of pregnancy. An increase in hepatic DG (diacylglycerol) 16:0_22:6 (by 243%) and significant decreases in Pla2G15 (0.4-fold) and Pla2G16 (0.6-fold) at day 20 of pregnancy, no changes in Lpcat1-4, and an abundant pool of hepatic pool PE (phosphatidylethanolamine) 16:0_22:6 suggest that plasma PC 16:0_22:6 is not being produced by fatty acyl remodeling during pregnancy. The increase in plasma PC 16:0_22:6 during pregnancy appears to be due to an increase in de novo synthesis of PC and both the CDP-choline and phosphatidylcholine methyltransferase pathways are implicated. There was also evidence suggesting channeling of DHA into PC and lipoprotein assembly may be occurring. Targeted research is necessary to confirm these findings, but the results of this study indicate metabolic adaptions to enable maternal/dam resiliency towards meeting the fetal/pup demand for DHA during pregnancy.

Dietary Reference Intakes based on chronic disease endpoints: outcomes from a case study workshop for omega 3's EPA and DHA.

Given the focus on developing Dietary Reference Intakes (DRIs) based on chronic disease risk reduction and recent research for omega-3 long chain PUFA since the last DRI review, the Canadian Nutrition Society convened a panel of stakeholders for a 1-day workshop in late 2019. Attendees discussed the new NASEM guidelines for establishing DRI values based on chronic disease risk endpoints and the strength of current evidence for EPA and DHA as it relates to the new guidelines. Novelty: Summarizes evidence and expert opinions regarding the potential for reviewing DRI values for EPA and DHA and cardiovascular disease risk and early development.

Does polymorphisms in PPAR and APOE genes modify associations between fatty acid desaturase (FADS), n-3 long-chain PUFA and cardiometabolic markers in 8-11-year-old Danish children?

n-3 Long-chain PUFA (LCPUFA) can improve cardiometabolic blood markers, but studies in children are limited. SNP in the FADS genes, which encode fatty acid desaturases, influence endogenous LCPUFA production. Moreover, SNP in genes that encode PPAR and apoE may modulate the effects of n-3 LCPUFA. We explored whether FADS polymorphisms were associated with blood cholesterol and TAG, insulin and glucose and whether polymorphisms in PPAR and APOE modified associations between FADS or n-3 LCPUFA status and the cardiometabolic blood markers. We measured fasting cholesterol and TAG, insulin, glucose and n-3 LCPUFA in 757 Danish 8-11-year-old children and genotyped SNP in FADS (rs1535 and rs174448), PPARG2 (rs1801282), PPARA (rs1800206) and APOE (rs7412+rs429358). Carriage of two FADS rs174448 major alleles was associated with lower TAG (P = 0·027) and higher HDL-cholesterol (P = 0·047). Blood n-3 LCPUFA was inversely associated with TAG and insulin in PPARG2 minor allele carriers and positively with LDL-cholesterol in major allele homozygotes (Pn-3 LCPUFA × rs180182 < 0·01). Associations between n-3 LCPUFA and cardiometabolic markers were not modified by APOE genotype (Pn-3 LCPUFA × APOE > 0·11), but interaction between FADS rs1535 and APOE showed that rs1535 major allele homozygotes who also carried APOE2 had higher HDL-cholesterol than all other genotype combinations (Prs1535 × APOE = 0·019, pairwise-P < 0·05). This indicates that FADS genotypes, which increase endogenous LCPUFA production, may beneficially affect children's cardiometabolic profile in a partly APOE-dependent manner. Also, the degree to which children benefit from higher n-3 LCPUFA intake may depend on their PPARG2 genotype.

Breast milk n-3 long-chain polyunsaturated fatty acids and blood pressure: an individual participant meta-analysis.

PURPOSE: It is controversial whether a higher intake of n-3 long-chain polyunsaturated fatty acids (n-3 LC PUFA) through breastfeeding is associated or not to a lower blood pressure (BP) during childhood. We aimed to clarify this point by undertaking a meta-analysis involving the data from seven European birth cohorts. METHODS: We searched https://www.birthcohort.net for studies that had collected breast milk samples, and had at least one BP measurement in childhood. Principal investigators were contacted, and all agreed to share data. One additional study was identified by contacts with the principal investigators. For each cohort, we analyzed the association of breast milk n-3 LC PUFAs with systolic and diastolic BP with linear mixed effects models or linear regression, and pooled the estimates with a random effects model. We also investigated age-specific and sex-specific associations. RESULTS: A total of 2188 participants from 7 cohorts were included. Overall, no associations between breast milk n-3 LC PUFAs and BP were observed. In the pooled analysis, each 0.1 wt% increment in breast milk docosahexaenoic acid (DHA) was associated with a 1.19 (95% CI - 3.31, 0.94) mmHg lower systolic BP. Associations were similar for boys and girls and at different ages. CONCLUSION: In this individual participant meta-analysis, we found no evidence for an association between breast milk n-3 LC PUFAs and BP.

The plasma lipidome of the Quaker parrot (Myiopsitta monachus).

Dyslipidemias and lipid-accumulation disorders are common in captive parrots, in particular in Quaker parrots. Currently available diagnostic tests only measure a fraction of blood lipids and have overall problematic cross-species applicability. Comprehensively analyzing lipids in the plasma of parrots is the first step to better understand their lipid metabolism in health and disease, as well as to explore new lipid biomarkers. The plasma lipidome of 12 Quaker parrots was investigated using UHPLC-MS/MS with both targeted and untargeted methods. Targeted methods on 6 replicates measured 432 lipids comprised of sterol, cholesterol ester, bile acid, fatty acid, acylcarnitine, glycerolipid, glycerophospholipid, and sphingolipid panels. For untargeted lipidomics, precursor ion mass-to-charge ratios were matched to corresponding lipids using the LIPIDMAPS structure database and LipidBlast at the sum composition or acyl species level of information. Sterol lipids and glycerophospholipids constituted the majority of plasma lipids on a molar basis. The most common lipids detected with the targeted methods included free cholesterol, CE(18:2), CE(20:4) for sterol lipids; PC(36:2), PC(34:2), PC(34:1) for glycerophospholipids; TG(52:3), TG(54:4), TG(54:5), TG(52:2) for glycerolipids; SM(d18:1/16:0) for sphingolipids; and palmitic acid for fatty acyls. Over a thousand different lipid species were detected by untargeted lipidomics. Sex differences in the plasma lipidome were observed using heatmaps, principal component analysis, and discriminant analysis. This report presents the first comprehensive database of plasma lipid species in psittacine birds and paves the way for further research into blood lipid diagnostics and the impact of diet, diseases, and drugs on the parrot plasma lipidome.

Effects of oily fish intake on cognitive and socioemotional function in healthy 8-9-year-old children: the FiSK Junior randomized trial.

BACKGROUND: Long-chain n-3 PUFAs (n-3 LCPUFAs) accrete in the brain during childhood and affect brain development. Randomized trials in children show inconsistent effects of n-3 LCPUFAs on cognitive and socioemotional function, and few have investigated effects of fish per se. OBJECTIVES: We aimed to investigate the effects of oily fish consumption on overall and domain-specific cognitive and socioemotional scores and explore sex differences. METHODS: Healthy 8-9-y-old children (n = 199) were randomly allocated to receive ∼300 g/wk oily fish or poultry (control) for 12 ± 2 wk. At baseline and endpoint, we assessed attention, processing speed, executive functions, memory, emotions, and behavior with a large battery of tests and questionnaires and analyzed erythrocyte fatty acid composition. RESULTS: One hundred and ninety-seven (99%) children completed the trial. Children in the fish group consumed 375 (25th-75th percentile: 325-426) g/wk oily fish resulting in 2.3 (95% CI: 1.9, 2.6) fatty acid percentage points higher erythrocyte n-3 LCPUFA than in the poultry group. The overall cognitive performance score tended to improve by 0.17 (95% CI: -0.01, 0.35) points in children who received fish compared with poultry, supported by n-3 LCPUFA dose dependency. This was driven mainly by fewer errors [-1.9 (95% CI: -3.4, -0.3)] in an attention task and improved cognitive flexibility measured as faster reaction time [-51 ms (95% CI: -94, -7 ms)] in a complex relative to a simple task ("mixing cost"). The fish intervention furthermore reduced parent-rated Strength and Difficulties Questionnaire total difficulties by -0.89 (95% CI: -1.60, -0.18) points mainly due to a -0.63 (95% CI: -1.11, -0.16) points reduction in internalizing problems that was reflected in tendency to a decrease in the overall socioemotional problems score of -0.13 (95% CI: -0.26, 0.01) points. The overall effects were similar in boys and girls. CONCLUSIONS: Oily fish dose-dependently improved cognitive function, especially attention and cognitive flexibility, and reduced socioemotional problems. The results support the importance of n-3 LCPUFAs for optimal brain function and fish intake recommendations in children.The trial was registered at www.clinicaltrials.gov as NCT02809508.