Mead Acid Research Articles

Effect of parenteral lipids on essential fatty acid deficiency in pediatric intestinal failure: A retrospective cohort study.

Pediatric patients with intestinal failure require long-term parenteral nutrition owing to impaired enteral nutrition absorption. A potential complication is essential fatty acid deficiency (EFAD), resulting from decreased linoleic and α-linolenic acid concentrations and defined by an increased triene:tetraene ratio (TTR; Mead acid:arachidonic acid). Historically, soybean oil lipid emulsion (SOLE) was the only commercially available parenteral lipid in the United States. Recently, a composite lipid emulsion (CLE) and fish oil lipid emulsion (FOLE) received US Food and Drug Administration approval. This study investigated whether lipid emulsion regimen impacts EFAD incidence in pediatric patients with intestinal failure. This study was a 10-year retrospective cohort study of pediatric patients with intestinal failure who received parenteral SOLE, CLE, or FOLE. The primary outcome was EFAD incidence, defined as a TTR ≥ 0.2. Secondary outcomes included TTR ≥ 0.05, cholestasis incidence, lipid dose effect on EFAD incidence, and fatty acid parameter differences. A total of 144 fatty acid profiles from 47 patients were reviewed. EFAD did not occur in any lipid emulsion group. There were no differences in the incidence of TTR ≥ 0.05 or cholestasis. The effect of dose could not be evaluated because of no EFAD incidence. Lastly, although each group had varied fatty acid parameters, none saw decreased essential fatty acid levels. This study found that, with close monitoring, the lipid emulsion regimen did not impact EFAD incidence. This suggests that FOLE and CLE do not increase EFAD risk compared with SOLE in pediatric patients with intestinal failure.

Effectiveness of grease interceptors in food service establishments for controlling fat, oil and grease deposition in the sewer system

The water industry worldwide experiences numerous sewer blockages each year, partially attributed to the accumulation of fat, oil and grease (FOG). Managing this issue involves various strategies, including the requirement for installation of grease interceptors (GIs) installation. However, the claimed efficacy of commercial GIs of eliminating 99 % of FOG has been questioned for many years because FOG deposit formation occurs despite food service establishments (FSEs) using GIs, therefore detailed understanding of FOG wastewater compositions and its removal by GIs is required. This study provides an insight into the key FOG components such as FOG particle size, metals and fatty acid (FA) profile in GI influent and effluent, and within the GI, at three different FSEs. Analysis of FAs identified substantial proportions of extra-long-chain FAs in the effluents, including arachidic (C20:0), behenic (C22:0), mead (C20:3), lignoceric (C24:0), and nervonic (C24:1) acids. In contrast, the household kitchen released palmitic (C16:0), oleic (C18:1) and linoleic (C18:2) acids. It was further observed that scums effectively remove the larger FOG particles, leaving only 10 % below 75.4 μm. Notably, FSEs which employed automatic dishwashers produced up to 80.4 % of particles ≤45 μm, whereas FSEs and household kitchen which used handwash sinks generated only 36.9 % and 26.3 % of particles ≤45 μm, respectively. This study demonstrated that the commercial GIs do not remove FOG entirely but clearly demonstrated that they discharge high concentrations of FOG with extra-long FFAs which were attributed to the occurrence of microbial activity and hydrolysis of triglycerides within the GI, potentially contributing to FOG deposition.

Associations Between Blood Nutritional Biomarkers and Cerebral Amyloid-β: Insights From the COGFRAIL Cohort Study.

Understanding the relationship between blood nutrients and neurodegeneration could contribute to devising strategies for preventing Alzheimer's disease. We investigated the associations between fatty acids, vitamins D, B6, B12, folate, homocysteine, and the cerebral load of amyloid β (Aβ). This cross-sectional study included 177 older adults (70-96 years, 65% female) with objective cognitive impairment, prefrail, or frail. Cerebral Aβ load was determined using positron emission tomography Standardized Uptake Value ratios. Fatty acids were assessed in erythrocytes, vitamins D and homocysteine in serum, and the other vitamins in plasma. Linear regression models corrected for multiple comparisons evaluated the associations between each nutrient and Aβ. The principal component factor followed by linear regression grouped the fatty acids strongly correlated (factor) and associated with Aβ. Higher concentrations of polyunsaturated fatty acids (PUFAs): clupanodonic acid (22:5n-3; β: -0.13; p = .001), mead acid (20:3n-9; β: -0.07; p = .036), and adrenic acid (22:4n-6; β: -0.05; p = .031) were associated with lower global Aβ load, whereas linoleic acid (18:2n-6) was associated with higher global Aβ load (β: 0.18; p = .042). Clupanodonic acid was inversely associated with Aβ in all cerebral regions except the thalamus. The factor composed of mead, clupanodonic, and arachidonic (20:4n-6) acids was associated with a lower global Aβ load (β: -0.02; p = .002). Some erythrocyte PUFAs were inversely associated with Aβ load in the brain, and most of them were metabolites of the essential fatty acids linoleic and α-linolenic. Given the cross-sectional design, these results must be carefully interpreted, and longitudinal studies are needed.

Maternal fatty acid status during pregnancy versus offspring inflammatory markers: a canonical correlation analysis of the MEFAB cohort.

The development of inflammatory lung disorders in children may be related to maternal fatty acid intake during pregnancy. We therefore examined maternal fatty acid (FA) status during pregnancy and its associations with inflammatory markers and lung conditions in the child by analyzing data from the MEFAB cohort using multivariate canonical correlation analysis (CCA). In the MEFAB cohort, 39 different phospholipid FAs were measured in maternal plasma at 16, 22 and 32 weeks of pregnancy, and at day of birth. Child inflammatory markers and self-reported doctor diagnosis of inflammatory lung disorders were assessed at 7 years of age. Using CCA, we found that maternal FA levels during pregnancy were significantly associated with child inflammatory markers at 7 years of age and that Mead acid (20:3n-9) was the most important FA for this correlation. To further verify the importance of Mead acid, we examined the relation between maternal Mead acid levels at the day of birth with the development of inflammatory lung disorders in children at age 7. After stratification for the child's sex, maternal Mead acid levels at day of birth were significantly related with self-reported doctor diagnosis of asthma and lung infections in boys, and bronchitis and total number of lung disorders in girls. Future studies should investigate whether the importance of Mead acid in the relation between maternal FA status and inflammation and lung disorders in the child is due to its role as biomarker for essential fatty acid deficiency or due to its own biological function as pro-inflammatory mediator.

The Effect of Fatty Acids and Meat Oils Combustion on PAH Formation in Smoke during Grilling Process


 
 
 
 Background: Oil droplets from foods can cause the formation of Polycyclic Aromatic Hydrocarbons (PAHs) in smoke and contaminate grilled food. The aim of this research was to examine the effect of the number of carbon atoms, degree of double bonds, and types of fatty acids on the formation of PAHs in smoke during grilling process.
 Methods: Four fatty acids consisting of palmitic acid, stearic acid, linoleic acid, and oleic acid, and three animal oils consisting of chicken skin oil, beef oil, and striped catfish oil had been studied. The smoke obtained during the combustion of fatty acids and animal oils was collected in a PUF/XAD-2/PUF absorption tube, and the analysis of 16 major PAHs was done using Gas Chromatography-Mass Spectroscopy (GC-MS). The experiments were conducted in three replicates.
 Results: Linoleic acid and oleic acid generated relatively higher concentrations of PAHs in the smoke, at 48.53 and 46.81 ppm, while stearic acid and palmitic acid provided PAHs in the smoke at 6.15 and 3.87 ppm. The rank of the highest PAH concentration levels in order of decreasing in smoke included striped catfish oil, chicken skin oil, and beef loin oil, with values of 50.22, 35.07, and 33.62 ppm, respectively. A variety of fatty acids were found in animal oils, but some fatty acids, such as arachidic acid (20:0), mead acid (20:3), behenic acid (22:0), erucic acid (22:1), cervonic acid (DHA) (22:6), lignoceric acid (24:0), and nervonic acid (24:1), were not found in chicken skin oil or beef oil. Fatty acids in the striped catfish oil had longer carbon chains (20:0, 20:3, 22:0, 22:1, 22:6, 24:0, 24:1) compared to other animal oils and a higher degree of double bonds, thus giving a higher PAHs concentration.
 Conclusion: It can be concluded that PAH concentration present in the smoke of animal oils depends on the number of carbon atoms, the degree of double bonds in the molecules, and the types of fatty acids.
 
 
 

Mead acid production by disruption of Δ12-desaturase gene in Mortierella alpina 1S-4

Mead acid (MA; 20:3ω9) is one of the ω9 series of polyunsaturated fatty acids (PUFAs). MA is used to inhibit the inflammation of joints and is applied to the medicinal or health food field. We aimed to construct MA-producing strains with disruption of the Δ12-desaturase gene (Δ12ds) via an efficient gene-targeting system using the lig4-disrupted strain of Mortierella alpina 1S-4 as the host. The transformants showed a unique fatty acid composition that only comprised ω9-PUFAs and saturated fatty acids, while ω6-and ω3-PUFAs were not detected, and the total composition of ω9-PUFAs, including oleic acid (18:1ω9), 18:2ω9, 20:1ω9, 20:2ω9, and MA, was up to 68.4% of the total fatty acids. The MA production in the Δ12ds-disruptant reached 0.10g/L (8.5%), which exceeded 0.050g/L (4.6%) in the conventional Δ12ds-defective mutant JT-180.

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

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. 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. 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 (β-1.4 FA%, 95%CI.-2.7;-0.1), n-6 LCPUFA (β-1.3 FA%, 95%CI.-1.3;-0.3), and AA (β-0.6 FA%, 95%CI.-1.0;-0.2). Age-adjusted height was negatively associated with the Mead acid:AA ratio (β-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. 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. ClinicalTrials.gov: NCT02907424.

Composite lipid emulsion use and essential fatty acid deficiency in pediatric patients with intestinal failure with high parenteral nutrition dependence: A retrospective cohort study.

Reports of essential fatty acid deficiency (EFAD) in patients receiving parenteral nutrition (PN) and a composite lipid (mixed oil intravenous lipid emulsion [MO ILE]) are predominantly when managed by lipid restriction. The objective of this study was to determine the prevalence of EFAD in patients with intestinal failure (IF) who are PN dependent without lipid restriction. We retrospectively evaluated patients, ages 0-17 years, followed by our intestinal rehabilitation program between November 2020 and June 2021 with PN dependency index (PNDI) of >80% on a MO ILE. Demographic data, PN composition, PN days, growth, and plasma fatty acid profile were collected. A plasma triene-tetraene (T:T) ratio >0.2 indicated EFAD. Summary statistics and Wilcoxon rank sum test evaluated to compare between PNDI category and ILE administration (grams/kilograms/day). P < 0.05 was considered significant. Twenty-six patients (median age, 4.1 years [interquartile range (IQR) = 2.4-9.6]) were included. The median duration of PN was 1367 days (IQR = 824-3195). Sixteen patients had a PNDI of 80%-120% (61.5%). Fat intake for the group was 1.7 g/kg/day (IQR = 1.3-2.0). The median T:T ratio was 0.1 (IQR = 0.1-0.2) with no values >0.2. Linoleic and arachidonic acid were low in 85% and 19% of patients, respectively; however, Mead acid was normal in all patients. This report is the largest to date on the EFA status of patients with IF on PN. These results suggest that, in the absence of lipid restriction, EFAD is not a concern when using MO ILEs in children receiving PN for IF.

Changes in nutrition and growth status in young children in the first 12 weeks of ivacaftor therapy

BackgroundHighly effective CFTR modulators improve nutritional status and are of particular importance among younger children experiencing rapid growth. This study was designed to examine CFTR modulator associated changes in nutritional and other extrapulmonary outcomes in children 4–24 months of age with ivacaftor treatment over 12 weeks. MethodsChildren 4–24 months were recruited from US and Canadian CF Centers. Eligible children were ivacaftor naïve and approved to start therapy. Anthropometrics, diet, sleeping energy expenditure (SEE), nutrition biomarkers, pancreatic status, serum and fecal calprotectin, serum bile acids, plasma fatty acids were measured. Changes from baseline at 6 and 12 weeks were examined using mixed effects linear regression modeling. ResultsFifteen participants enrolled (40% male). Weight-for-age z-scores increased at 6 (p = 0.03) and 12 weeks ivacaftor therapy (p<0.001) compared to baseline. Plasma docosatetraenoic acid (DTA), total saturated fatty acids increased at 6 weeks (p = 0.02) and 12 weeks (p = 0.009). At 12 weeks, serum CO2 concentration decreased (p = 0.002), serum urea nitrogen increased (p = 0.01) and fecal elastase increased (p = 0.02) compared to baseline. Bile acids, deoxycholic acid increased (p = 0.03) and ursodeoxycholic acid decreased (p = 0.02) after 12 weeks. Plasma total fatty acids, palmitic acid, mead, and docosatetraenoic acid (DTA) increased after 12 weeks (p = 0.02, p = 0.002 and p = 0.04, respectively). Plasma total saturated fatty acids increased at 6 weeks (p = 0.02) and 12 weeks (p = 0.009). Dietary intake (p = 0.04) and percent kcal from protein (p = 0.04) increased after 12 weeks compared to baseline. ConclusionsOverall, younger children experienced favorable changes in nutritional and growth status in the first 12 weeks of ivacaftor therapy.

Oxygen-induced pathological angiogenesis promotes intense lipid synthesis and remodeling in the retina

The retina is a notable tissue with high metabolic needs which relies on specialized vascular networks to protect the neural retina while maintaining constant supplies of oxygen, nutrients, and dietary essential fatty acids. Here we analyzed the lipidome of the mouse retina under healthy and pathological angiogenesis using the oxygen-induced retinopathy model. By matching lipid profiles to changes in mRNA transcriptome, we identified a lipid signature showing that pathological angiogenesis leads to intense lipid remodeling favoring pathways for neutral lipid synthesis, cholesterol import/export, and lipid droplet formation. Noteworthy, it also shows profound changes in pathways for long-chain fatty acid production, vital for retina homeostasis. The net result is accumulation of large quantities of mead acid, a marker of essential fatty acid deficiency, and a potential marker for retinopathy severity. Thus, our lipid signature might contribute to better understand diseases of the retina that lead to vision impairment or blindness.

New Perspectives on the Associations between Blood Fatty Acids, Growth Parameters, and Cognitive Development in Global Child Populations.

Malnutrition is prevalent in low-middle-income countries (LMICs), but it is usually clinically diagnosed through abnormal anthropometric parameters characteristic of protein energy malnutrition (PEM). In doing so, other contributors or byproducts of malnutrition, notably essential fatty acid deficiency (EFAD), are overlooked. Previous research performed mainly in high-income countries (HICs) shows that deficiencies in essential fatty acids (EFAs) and their n-3 and n-6 polyunsaturated fatty acid (PUFA) byproducts (also known as highly unsaturated fatty acids or HUFAs) lead to both abnormal linear growth and impaired cognitive development. These adverse developmental outcomes remain an important public health issue in LMICs. To identify EFAD before severe malnutrition develops, clinicians should perform blood fatty acid panels to measure levels of fatty acids associated with EFAD, notably Mead acid and HUFAs. This review demonstrates the importance of measuring endogenous fatty acid levels for measuring fatty acid intake in various child populations in LMICs. Featured topics include a comparison of fatty acid levels between global child populations, the relationships between growth and cognition and PUFAs and the possible mechanisms driving these relationships, and the potential importance of EFAD and HUFA scores as biomarkers of overall health and normal development.

Mead acid inhibits retinol-induced irritant contact dermatitis via peroxisome proliferator-activated receptor alpha.

Retinol is widely used in topical skincare products to ameliorate skin aging and treat acne and wrinkles; however, retinol and its derivatives occasionally have adverse side effects, including the induction of irritant contact dermatitis. Previously, we reported that mead acid (5,8,11-eicosatrienoic acid), an oleic acid metabolite, ameliorated skin inflammation in dinitrofluorobenzene-induced allergic contact hypersensitivity by inhibiting neutrophil infiltration and leukotriene B4 production by neutrophils. Here, we showed that mead acid also suppresses retinol-induced irritant contact dermatitis. In a murine model, we revealed that mead acid inhibited keratinocyte abnormalities such as keratinocyte hyperproliferation. Consistently, mead acid inhibited p38 MAPK (mitogen-activated protein kinase) phosphorylation, which is an essential signaling pathway in the keratinocyte hyperplasia induced by retinol. These inhibitory effects of mead acid were associated with the prevention of both keratinocyte hyperproliferation and the gene expression of neutrophil chemoattractants, including Cxcl1 and Cxcl2, and they were mediated by a PPAR (peroxisome proliferator-activated receptor)-α pathway. Our findings identified the anti-inflammatory effects of mead acid, the use of which can be expected to minimize the risk of adverse side effects associated with topical retinoid application.

Oxylipin status, before and after LC n-3 PUFA supplementation, has little relationship with skeletal muscle biology in older adults at risk of sarcopenia

IntroductionOxylipins form endogenously via the oxygenation of long-chain polyunsaturated fatty acids (LC PUFA). Several oxylipins are highly bioactive molecules and are believed to be key mediators of LC PUFA metabolism in the body. However, little is known in relation to whether oxylipins mediate alterations in skeletal muscle mass and function. The objective of this study was to determine if a relationship exists between the oxylipin profile and skeletal muscle biology in healthy older adults at risk of sarcopenia and determine if this changes in response to LC n-3 PUFA supplementation. Materials and methodsThis exploratory study investigated the baseline correlations between LC n-3, n-6 and n-9 PUFA-derived oxylipins and markers of muscle biology. For this, the concentration of 79 free (i.e., non-esterified) oxylipins was quantified in human plasma by liquid chromatography-mass spectrometry (LC-MS) and retrospectively correlated to phenotypic outcomes obtained pre-intervention from the NUTRIMAL study (n = 49). After examining the baseline relationship, the potential effect of supplementation (LC n-3 PUFA or an isoenergetic control made of high-oleic sunflower and corn oil) was evaluated by correlating the change in oxylipins concentration and the change in markers of skeletal muscle biology. The relationship between oxylipins pre- and post-intervention and their parent PUFA were also examined. ResultsAt baseline, the hydroxy product of mead acid (n-9 PUFA), 5-HETrE, was negatively correlated to the phenotypic parameters appendicular lean mass index (ALMI) (p = 0.003, r=-0.41), skeletal muscle mass index (SMMI) (p = 0.001, r=-0.46), handgrip strength (HGS) (p<0.001, r = 0.48) and isometric knee extension (p<0.001, r=-0.48). Likewise, LC n-6 PUFA hydroxy‑PUFA were negatively correlated to HGS (i.e., 12-HETrE, p = 0.002, r=-0.42, and 5- and 11-HETE, p = 0.006, r=-0.47 and p<0.001, r=-0.50 respectively), single leg stand time (i.e., 12-HETrE, p = 0.006, r=-0.39 and 16-HETE, p = 0.002, r=-0.43), and five-time-sit-to-stand test (FTST) performance (16-HETE, p = 0.006, r = 0.39), and positively correlated to gait speed (i.e., 12-HETrE, p = 0.007, r = 0.38 and 16-HETE, p = 0.006, r = 0.39). LC n-3 PUFA supplementation increased eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) derived oxylipins and reduced n-6 PUFA derived oxylipins. Parameters of skeletal muscle mass and strength were not significantly altered in either LC n-3 PUFA or placebo groups. Changes in plasma oxylipins concentrations were closely related to changes in their parent PUFA, assessed in the erythrocyte membrane, but were not associated with any changes in skeletal muscle parameters. Discussion and conclusionAt baseline, the status n-9 (5-HETrE) and n-6 PUFA derivates [12-HETrE, and 5-, 11- and 16-HETE], but not n-3 PUFA derived oxylipins, were associated with poor skeletal muscle health parameters (i.e., mass and strength). However, these correlations were no longer present when correlating relative changes from pre to post timepoints. An independent cohort validation is needed to explore baseline correlations further. Further research is warranted to assess other biological mechanisms by which LC n-3 PUFA might affect muscle biology.

Futile cycle of β-oxidation and de novo lipogenesis are associated with essential fatty acids depletion in lipoatrophy

Total absence of adipose tissue (lipoatrophy) is associated with the development of severe metabolic disorders including hepatomegaly and fatty liver. Here, we sought to investigate the impact of severe lipoatrophy induced by deletion of peroxisome proliferator-activated receptor gamma (PPARγ) exclusively in adipocytes on lipid metabolism in mice. Untargeted lipidomics of plasma, gastrocnemius and liver uncovered a systemic depletion of the essential linoleic (LA) and α-linolenic (ALA) fatty acids from several lipid classes (storage lipids, glycerophospholipids, free fatty acids) in lipoatrophic mice. Our data revealed that such essential fatty acid depletion was linked to increased: 1) capacity for liver mitochondrial fatty acid β-oxidation (FAO), 2) citrate synthase activity and coenzyme Q content in the liver, 3) whole-body oxygen consumption and reduced respiratory exchange rate in the dark period, and 4) de novo lipogenesis and carbon flux in the TCA cycle. The key role of de novo lipogenesis in hepatic steatosis was evidenced by an accumulation of stearic, oleic, sapienic and mead acids in liver. Our results thus indicate that the simultaneous activation of the antagonic processes FAO and de novo lipogenesis in liver may create a futile metabolic cycle leading to a preferential depletion of LA and ALA. Noteworthy, this previously unrecognized cycle may also explain the increased energy expenditure displayed by lipoatrophic mice, adding a new piece to the metabolic regulation puzzle in lipoatrophies.

The fatty acid imbalance of cystic fibrosis exists at birth independent of feeding in pig and ferret models.

Persons with cystic fibrosis (CF) exhibit a unique alteration of fatty acid composition, marked especially among polyunsaturates by relative deficiency of linoleic acid and excess of Mead acid. Relative deficiency of docosahexaenoic acid is variably found. However, the initial development of these abnormalities is not understood. We examined fatty acid composition in young CF ferrets and pigs, finding abnormalities from the day of birth onward including relative deficiency of linoleic acid in both species. Fatty acid composition abnormalities were present in both liver and serum phospholipids of newborn CF piglets even prior to feeding, including reduced linoleic acid and increased Mead acid. Serum fatty acid composition evolved over the first weeks of life in both non-CF and CF ferrets, though differences between CF and non-CF persisted. Although red blood cell phospholipid fatty acid composition was normal in newborn animals, it became perturbed in juvenile CF ferrets including relative deficiencies of linoleic and docosahexaenoic acids and excess of Mead acid. In summary, fatty acid composition abnormalities in CF pigs and ferrets exist from a young age including at birth independent of feeding and overlap extensively with the abnormalities found in humans with CF. That the abnormalities exist prior to feeding implies that dietary measures alone will not address the mechanisms of imbalance.

Plasma Fatty Acid Composition Is Associated with Histological Findings of Nonalcoholic Steatohepatitis.

The relationship between advanced nonalcoholic steatohepatitis (NASH) and plasma fatty acid composition remains unknown. We aimed to examine the plasma fatty acid composition in biopsy-confirmed nonalcoholic fatty liver disease (NAFLD) and evaluate the relationship between histological findings and fatty acid composition. Overall, 235 patients (134 women) with NAFLD were enrolled. Comprehensive blood chemistry tests and histological examinations of liver samples were conducted. Multivariate analyses adjusted for age, sex, body mass index, alanine aminotransferase, hemoglobin A1c, creatinine, total cholesterol, triglyceride, and NAFLD Activity Score values showed that lower levels of arachidic, behenic, α-linolenic, eicosatetraenoic, docosapentaenoic, and docosahexaenoic acids and higher levels of mead acid were associated with fibrosis stage 3–4. Furthermore, higher lauric acid, myristic acid, and palmitic acid levels and monounsaturated fatty acids such as palmitoleic acid and oleic acid were significantly associated with high NAS in analyses adjusted for the same factors and fibrosis stage. The plasma fatty acid composition was associated with the histological evidence of NASH. Increased synthesis of fatty acids is associated with NASH; insufficient intake of n-3 essential fatty acids and reduced elongation of fatty acids are associated with fibrosis in NASH. These features may help clinicians to understand and treat advanced NASH cases.

Effects of early lactation body condition loss in dairy cows on serum lipid profiles and on oocyte and cumulus cell transcriptomes.

The objective of this study was to determine the effect of early lactation body condition (BC) loss in multiparous dairy cows on serum lipids and the effect of these changes on oocyte and cumulus cell transcriptomes. Body condition loss in dairy cattle after parturition is associated with reduced fertility and increased pregnancy loss. The complex interplay between BC, nutrition, dry matter intake, milk production, and time of calving has presented a barrier to understanding mechanisms leading to reduced fertility. We identified cows that lost BC (L group; n = 10) or maintained or gained BC (M/G group; n = 8) during the first 27 to 33 d in milk and investigated changes in serum fatty acids and oocyte and cumulus cell transcriptomes at 75 to 81 d in milk. The L group had increased serum levels of nonesterified fatty acids and mead acid, and reduced serum levels of petroselaidic acid and behenic acid. Transcriptome analyses revealed 38 differentially expressed genes (DEG) in oocytes and 71 DEG in cumulus cells of L (n = 3) compared with M/G group (n = 3). Network analysis connected serum fatty acid changes to downstream effects including reduced inflammatory response and mitochondrial membrane depolarization, increased production of reactive oxygen species, and functions related to fatty acid metabolism and cytoplasmic organization in oocytes. These effects were associated with predicted effects on signaling in oocytes through calcium, insulin, O-GlcNAcase (OGA), fibroblast growth factor receptor 4 (FGF4R), peroxisome proliferator activated receptor gamma coactivator 1 α (PPARGC1A), and phospholipase D2 (PLD2) pathways, with a connection to the cumulus cell via calcium signaling. These results connect BC loss following parturition to changes in serum lipid levels, and changes potentially affecting oocyte quality; thus, these results provide new insight into mechanism of reduced fertility.

119 Change in Serum Total Lipid Profiles in Dogs Supplemented with Camelina, Flaxseed, or Canola oil for 16 Weeks

Abstract There are few data describing the effects of different oils on fatty acid (FA) metabolism in dogs. Our objectives were to assess the effects of camelina (CAM), flaxseed (FLAX), and canola oil (OLA) on the serum total lipid FA profiles over a 16-week feeding study. Thirty healthy, adult dogs of various breeds [17 females, 13 males; 7.2±3.1 years and 27.4±14.0 kg (mean±SD)] underwent a 4-week dietary wash-in period on a commercial, low-fat kibble top dressed with 8.2g sunflower oil/100g food intake. Dogs were blocked by breed, age, and size, and assigned to receive CAM, FLAX, or OLA for 16-weeks at the same dose as wash-in. Serum total FA were measured using gas chromatography from dogs at baseline and week 16. Data were analyzed with ANOVA using PROC GLIMMIX of SAS. In all treatments, the final percent area of pooled and individual omega-3 (n-3) and omega-6 (n-6) FAs were inversely related, with n-3 being greater at week 16 and n-6 less at week 16 compared with baseline (p&amp;lt; 0.05). Conversely, dihomo-γ-linolenic acid showed accumulation at week 16 and docosahexaenoic acid was less at week 16 than baseline for all treatments (p&amp;lt; 0.05). Stearidonic acid was greater in FLAX than OLA but both were similar to CAM, and α-linolenic differed among all treatments (FLAX &amp;gt;CAM &amp;gt;OLA) (p&amp;lt; 0.05). Eicosadienoic acid was less in FLAX than CAM and OLA (p&amp;lt; 0.05). Omega-9 FA were greater at week 16 for all treatments and individual FAs (p&amp;lt; 0.05). Eicosaenoic and mead acid were greater in CAM than FLAX and OLA, and oleic acid was greater in FLAX than OLA, but similar to CAM (p&amp;lt; 0.05). Differences among dogs fed camelina, flax, and canola oils were due to the inherent FA concentrations of the oil and suggest all oils are suitable for increasing serum n-3 concentrations.

Severe Asymptomatic Essential Fatty Acid Deficiency (EFAD) in a Patient Enrolled in a Quality Improvement Project for HPN Patients (QIP-PN)

ObjectivesIntroduction. A 97-year-old, 47 kg female with a history of dysphasia, and failed enteral feeding was on HPN for 35 months. PN provided 150 grams dextrose, 75 grams amino acids, electrolytes, MVI and trace elements. Intravenous lipid emulsion (ILE) was held because liver dysfunction and line infections.MethodsThe patient enrolled in Amerita QIP-PN program. Essential fatty acid and trace element levels were obtained.ResultsSevere deficiencies of linoleic (c18:2w6; 524.3; (nl) 2653.4–6130.3 umol/L) and ἀ-linolenic acids (c18:3w3; 4.12; nl 26.1–150.1) were detected. Eicosatrienoic (Mead) acid (c20:3w9) was markedly elevated at 135.33 (nl 10.3–41.3). The eicosatrienoic to arachidonic acid (triene to tetraene) ratio was markedly elevated (0.27; nl 0.02–0.05). Stearic (267.2; nl 590.2 – 1377.2) and arachidic (8.86; nl 16.8 – 38.5) acids were low. Total polyunsaturated (1.6; nl 3.57 – 8.11) and total n-6 fatty acids (1.3; nl 3.3 – 7.1) were low. Seven fatty acid levels were elevated, apparently from de novo lipogenesis in the presence of insulin: myristic = 299.15 (nl 39.4 – 258.2), hexadecanoic = 300.41(nl 19.82 – 59.93), palmetoleic = 1197.60 (nl 68.5 – 570.2), vaccenic = 458.11 (nl 84.82 – 260.8), docosapentanoic = 32.8 (nl 9.2–32.1), docosenoic = 20.88 (nl 5.73 – 11.92). Interventions. Four-oil ILE was added as 20 grams once weekly, providing ∼4 grams of linoleic and ∼0.5 grams of ἀ-linolenic acids. Follow up free fatty acids showed normalization of ἀ-linolenic (27.07) and improvement in linoleic (889.74) and mead (60.34) acids. The triene to tetraene ratio improved to 0.17.ConclusionsAn elevated Mead acid level and elevated triene to tetraene ratio confirmed severe EFAD. Mead acid is produced from the elongation of oleic acid (n-9). The n-3, n-6, and n-9 fatty acids all compete for the same desaturases. But the desaturase enzymes have a preference for the fatty acids based on their n-terminal structure. The sequence is n-3 > n-6 > n-9. Therefore, increased Mead acid (20:3n-9) synthesis occurs only with very low availability of n-3 and n-6 fatty acids. In severe EFAD, Mead acid serves as a precursor to specific prostaglandins and leukotrienes via the cycloxygenase and lipoxygenase pathways. This case highlights the value of the QIP-PN in identifying EFAD in long-term HPN patients.Funding SourcesNone.

The Effects of Chemotherapy on Circulating Plasma Omega-9, Omega-3 Fatty Acids and Plasmalogen in Breast Cancer Patients

ObjectivesChemotherapy produces long-term cognitive impairment (CICI) in ∼30% of those receiving solid tumor treatment. Our previous results revealed a positive correlation between doxorubicin treatment and murine hippocampal concentrations of omega-9 fatty acids, relative to untreated controls. Our objective was to measure these and other structurally analogous fatty acids in human plasma following breast-cancer treatment, to determine if they might serve as biomarkers and/or nutritional targets during treatment. MethodsSerum samples were collected from patients (n = 51) at ≥ 2 of 3 visits: immediately prior to standard adjuvant and neo-adjuvant chemotherapy for breast cancer (baseline), prior to the third cycle of chemotherapy, and 6 months after chemotherapy termination. Lipophilic extracts of serum were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) to quantify eicosapentaenoic acid (EPA), Docosahexaenoic acid (DHA), linoleic acid, oleic acid, mead acid, gondoic acid, erucic acid, nervonic acid and PE(P-18:0/22:6) (plasmalogen). Linear models assessed the impact of visit on fatty acid concentrations, with a fixed intercept used for each subject. A P < 0.05 for chemotherapy was considered significant. ResultsChemotherapy significantly increased plasma concentrations of gondoic, erucic, nervonic acids and plasmalogen (with no effect on the other fatty acids tested). Six months following chemotherapy, concentrations of gondoic, erucic, nervonic acids and plasmalogen approached baseline concentrations. ConclusionsBreast cancer chemotherapy significantly increased plasma concentrations of omega-9 fatty acids previously reported as increased in subjects with increasing severity of cognitive impairment and Alzheimer’s disease. Ongoing work includes correlating the concentrations of these fatty acids with measures of memory and cognition. Future investigations will determine if these compounds may serve as nutritional targets for dietary interventions prior to or during chemotherapy treatment, and/or serve as objective biomarkers of CICI. Funding SourcesThe Ohio State University Stefanie Spielman Breast Cancer Center Kroger Fund, Pelotonia, NIH R01CA189947, NIH Award Number Grant P30 CA016058, OSU, and OSUCCC.