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Iron deficiency in pregnancy is related to many poor health outcomes, including anemia and low birth weight. A small number of previous studies have identified maternal body mass index (BMI) as a potential risk factor for poor iron status. Our objective was to examine the association between pre-pregnancy BMI, iron status, and anemia in a nationally representative sample of US adult women. We used data from the National Health and Nutrition Examination Survey (NHANES; 1999-2010) for pregnant women ages 18-49 years (n = 1156). BMI (kg/m2) was calculated using pre-pregnancy weight (self-reported) and height (measured at examination). Iron deficiency (ID) was defined as total body iron (calculated from serum ferritin and transferrin receptor using Cook's equation) < 0 mg/kg and anemia as hemoglobin < 11 g/dL. Associations were examined using weighted linear and Poisson regression models, adjusted for confounders (age, race/ethnicity, education, and trimester). Approximately 14% of pregnant women had ID and 8% had anemia in this sample. Ferritin and total body iron trended slightly lower (p = 0.12, p = 0.14) in women with pre-pregnancy BMI in the normal and overweight categories compared to the underweight and obese categories; hemoglobin concentrations were similar across BMI groups (p = 0.76). There were no differences in the prevalence of ID or anemia in women with pre-pregnancy overweight and obesity (ID: overweight, adjusted prevalence ratio (PR) = 1.27, 95%CI: 0.89-1.82; obesity, PR = 0.75, 95%CI: 0.39-1.45; anemia: overweight, PR = 1.08, 95%CI: 0.53-2.19; obesity, PR = 0.99, 95%CI: 0.49-2.01) compared to women with a normal BMI. Findings from these US nationally representative data indicate that total body iron, serum hemoglobin, ID, and anemia in pregnancy do not differ by pre-pregnancy BMI. Since ID and anemia during pregnancy remain significant public health concerns, NHANES should consider measuring current iron status in upcoming cycles., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ciulei et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Vitamin B12, or cobalamin, is an essential nutrient required for diverse physiological functions secondary to its role as a critical cofactor for two mammalian enzymes, methionine synthase and methylmalonyl-CoA mutase. While essential throughout all life stages, several pathways that require vitamin B12, including hematopoiesis, myelination, and DNA/histone methylation, are particularly critical during pregnancy and fetal development. This narrative review aims to describe vitamin B12 in pregnancy, with emphasis on the placenta's role in ensuring adequate nutrition of the fetus and impacts of vitamin B12 deficiency on placental development and function. Our literature search included preclinical model systems and human cohorts and interventions. Our review identified evidence of B12 deficiency resulting in impaired placental development, greater placental inflammation, and modulation of placental docosahexaenoic acid concentration, collectively suggestive of vitamin B12 deficiency as a determinant of both maternal and fetal health outcomes. Heterogeneity in study design complicated generalization of findings. Future studies should consider selecting a B12 marker that is relatively stable across pregnancy, such as holotranscobalamin, while accounting for important confounders such as maternal folate., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Amrita Arcot et al.)

Aberrant high-density lipoprotein (HDL) function is implicated in inflammation-associated pathologies. While HDL ABCA1-mediated reverse cholesterol and phospholipid transport are well described, the movement of pro-/anti-inflammatory lipids has not been explored. HDL phospholipids are the largest reservoir of circulating arachidonic acid-derived oxylipins. Endotoxin-stimulation activates inflammatory cells leading to hydroxyeicosatetraenoic acid (HETE) production, oxylipins which are involved in inflammatory response coordination. Active signaling in the non-esterified (NE) pool is terminated by sequestration of HETEs as esterified (Es) forms and degradation. We speculate that an ABCA1-apoA-I-dependent efflux of HETEs from stimulated cells could regulate intracellular HETE availability. Here we test this hypothesis both in vitro and in vivo. In endotoxin-stimulated RAW-264.7 macrophages preloaded with d8-arachidonic acid we use compartmental tracer modeling to characterize the formation of HETEs, and their efflux into HDL. We found that in response to endotoxin: I) Cellular NE 12-HETE is positively associated with MCP-1 secretion (p<0.001); II) HETE transfer from NE to Es pools is ABCA1-depedent (p<0.001); III) Cellular Es HETEs are transported into media when both apoA-I and ABCA1 are present (p<0.001); IV) The stimulated efflux of HETEs >> arachidonate (p<0.001). Finally, in endotoxin challenged humans (n=17), we demonstrate that intravenous lipopolysaccharide (0.6 ng/kg body weight) resulted in accumulation of 12-HETE in HDL over a 168-hour follow-up. Therefore, HDL can suppress inflammatory responses in macrophages by regulating intracellular HETE content in an apoA-I/ABCA1 dependent manner. The described mechanism may apply to other oxylipins and explain anti-inflammatory properties of HDL. This newly defined HDL property opens new doors for the study of lipoprotein interactions in metabolic diseases.

Fatty acids (FA) differ in their transfer efficiencies and metabolic partitioning and lactating cows provide a robust model to investigate kinetics of FA transport. The objective was to compare kinetics of n-3 polyunsaturated FA (PUFA) trafficking through plasma and into milk. In the first experiment, ten ruminally cannulated multiparous Holstein cows were used in a crossover design with 7 d periods. Cows were milked at 6 h intervals and abomasal treatments provided a single dose of 80.1 g of α-linolenic acid as free FA (ALA-FFA) or 45.5 g EPA and 32.9 g DHA (LCn3-FFA). Transfer of n-3 PUFA to milk was nearly 50% higher for ALA-FFA than LCn3-FFA (48.2 and 32.7% of the bolus) and fit a bi-exponential model. Rapid transport of n-3 PUFA, assumed to be directly through chylomicrons, was nearly twice as high in ALA-FFA than LCn3-FFA and the subsequent slow transport, assumed to be indirect transfer through tissue recycling, was over 2.5-fold higher in LCn3-FFA than in ALA-FFA. Plasma analysis revealed LCn3-FFA enriched phospholipids and cholesterol esters, which had a slow clearance. In the second experiment, 4 cows received a bolus of a mixture of ALA, EPA, and DHA prepartum while not lactating and around d 10, 55, and 225 of lactation. Transfer of ALA to milk did not differ between stages of lactation, but DHA was lower in early compared to mid and late lactation. In conclusion, dietary ALA is rapidly and efficiently transferred to milk in cows while EPA and DHA are rapidly incorporated into plasma or tissue fractions not available to the mammary gland. This demonstrates clear differences in trafficking and partitioning of n-3 PUFA that ultimately impact tissue and organelle enrichment with implications for effective doses., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kevin Harvatine reports financial support was provided by National Institute of Food and Agriculture., (Copyright © 2023. Published by Elsevier Ltd.)

Oxylipins are produced enzymatically from polyunsaturated fatty acids, are abundant in triglyceride-rich lipoproteins (TGRLs), and mediate inflammatory processes. Inflammation elevates TGRL concentrations, but it is unknown if the fatty acid and oxylipin compositions change. In this study, we investigated the effect of prescription ω-3 acid ethyl esters (P-OM3; 3.4 g/d EPA + DHA) on the lipid response to an endotoxin challenge (lipopolysaccharide; 0.6 ng/kg body weight). Healthy young men (N = 17) were assigned 8-12 weeks of P-OM3 and olive oil control in a randomized order crossover study. Following each treatment period, subjects received endotoxin challenge, and the time-dependent TGRL composition was observed. Postchallenge, arachidonic acid was 16% [95% CI: 4%, 28%] lower than baseline at 8 h with control. P-OM3 increased TGRL ω-3 fatty acids (EPA 24% [15%, 34%]; DHA 14% [5%, 24%]). The timing of ω-6 oxylipin responses differed by class; arachidonic acid-derived alcohols peaked at 2 h, while linoleic acid-derived alcohols peaked at 4 h (p int  = 0.006). P-OM3 increased EPA alcohols by 161% [68%, 305%] and DHA epoxides by 178% [47%, 427%] at 4 h compared to control. In conclusion, this study shows that TGRL fatty acid and oxylipin composition changes following endotoxin challenge. P-OM3 alters the TGRL response to endotoxin challenge by increasing availability of ω-3 oxylipins for resolution of the inflammatory response., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Obesity is associated with chronic inflammation and is a risk factor for insufficient milk production. Inflammation-mediated suppression of LPL could inhibit mammary uptake of long-chain fatty acids (LCFAs; >16 carbons)., Objectives: In an ancillary case-control analysis, we investigated whether women with low milk production despite regular breast emptying have elevated inflammation and disrupted transfer of LCFAs from plasma into milk., Methods: Data and specimens from a low milk supply study and an exclusively breastfeeding control group were analyzed, with milk production measured by 24-h test-weighing at 2-10 wk postpartum. Low milk supply groups were defined as very low (VL; <300 mL/d; n = 23) or moderate (MOD; ≥300 mL/d; n = 20) milk production, and compared with controls (≥699 mL/d; n = 18). Serum and milk fatty acids (weight% of total) were measured by GC, serum and milk TNF-α by ELISA, and serum high-sensitivity C-reactive protein (hsCRP) by clinical analyzer. Group differences were assessed by linear regression models, chi-square exact tests, and Kruskal-Wallis nonparametric tests., Results: VL cases, as compared with MOD cases and controls, had higher prevalence of elevated serum hsCRP (>5 mg/L; 57%, 15%, and 22%, respectively; P = 0.004), detectable milk TNF-α (67%, 32%, and 33%, respectively; P = 0.04), and obesity (78%, 40%, and 22%, respectively; P = 0.003). VL cases had lower mean ± SD LCFAs in milk (60% ± 3%) than MOD cases (65% ± 4%) and controls (66% ± 5%) (P < 0.001). Milk and serum LCFAs were strongly correlated in controls (r = 0.82, P < 0.001), but not in the MOD (r = 0.25, P = 0.30) or VL (r = 0.20, P = 0.41) groups (Pint < 0.001)., Conclusions: Mothers with very low milk production have significantly higher obesity and inflammatory biomarkers, lower LCFAs in milk, and disrupted association between plasma and milk LCFAs. These data support the hypothesis that inflammation disrupts normal mammary gland fatty acid uptake. Further research should address impacts of inflammation and obesity on mammary fatty acid uptake for milk production., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

BACKGROUND: There is limited research evaluating patient acceptability of medication formulations in the treatment of acute agitation. This study assessed patient acceptability of medication formulations (tablet, orally-dissolving-tablet [ODT], liquid, intramuscular injection [IM], inhaled device [INH]) for the treatment of acute agitation and examined correlating factors. METHODS: Adults with psychotic illness or bipolar disorder receiving emergency or inpatient services at an inpatient psychiatric facility in Kansas City, Missouri were included. Participants viewed a presentation on medication formulations for acute agitation and were surveyed on acceptability (measured on a five-point Likert scale). The primary outcome variable was the attitudinal measurement of acceptability of each formulation in correlation with the severity of agitation for use in themselves and other patients. RESULTS: One hundred participants completed the survey. Participants rated the following: (1) This medication formulation would be acceptable to treat mild agitation in themselves and others (oral tablet 85% and 48%; ODT 82% and 55%; liquid 74% and 51%; IM 53% and 74%; INH 78% and 72%); and (2) This medication formulation would be acceptable to treat severe agitation in themselves and others (oral tablet 75% and 52%; ODT 74% and 53%; liquid 66% and 53%; IM 61% and 67%; INH 77% and 72%). For treating mild agitation, participants preferred tablets and ODTs to the IM (p < 0.05) and the INH to liquid or IM (p < 0.05), for themselves; and oral formulations were preferred to the IM (p < 0.05) for other patients. For severe agitation in themselves and others, preference for the INH and IM versus oral formulations (p < 0.05) was significant, with no difference between the INH and IM (p > 0.05). CONCLUSIONS: The proportion of responses preferring oral formulations was higher than IM and INH. Dosage formulation acceptability differed depending on the severity of agitation and intended recipient of the medication.

Oxylipins are oxygenated metabolites of fatty acids that share several similar biochemical characteristics and functions to fatty acids including transport and trafficking. Oxylipins are most commonly measured in the non-esterified form which can be found in plasma, free or bound to albumin. The non-esterified form, however, reflects only one of the possible pools of oxylipins and is by far the least abundant circulating form of oxylipins. Further, this fraction cannot reliably be extrapolated to the other, more abundant, esterified pool. In cells too, esterified oxylipins are the most abundant form, but are seldom measured and their potential roles in signaling are not well established. In this review, we examine the current literature on experimental oxylipin measurements to describe the lack in reporting the esterified oxylipin pool. We outline the metabolic and experimental importance of esterified oxylipins using well established roles of fatty acid trafficking in non-esterified fatty acids and in esterified form as components of circulating lipoproteins. Finally, we use mathematical modeling to simulate how exchange between cellular esterified and unesterified pools would affect intracellular signaling.. The explicit inclusion of esterified oxylipins along with the non-esterified pool has the potential to convey a more complete assessment of the metabolic consequences of oxylipin trafficking.

Chronic low-grade inflammation can be associated with obesity or subclinical mastitis (SCM), which is associated with poor infant growth in low- to middle-income country settings. It is unknown what physiological mechanisms are involved in low milk supply, but our research group has shown that mothers with low milk supply have higher inflammatory markers. Studies investigating oxylipin signaling have the potential to help explain mechanisms that mediate the impacts of inflammation on milk production. Animal studies have reported various elevated oxylipins during postpartum inflammation, mastitis, and mammary involution in ruminant models. Several investigations have quantified oxylipins in human milk, but very few studies have reported circulating oxylipin concentrations during lactation. In addition, there are technical considerations that must be addressed when reporting oxylipin concentrations in human milk. First, the majority of milk oxylipins are esterified in the triglyceride pool, which is not routinely measured. Second, total milk fat should be considered as a covariate when using milk oxylipins to predict outcomes. Finally, storage and handling conditions of milk samples must be carefully controlled to ensure accurate milk oxylipin quantitation, which may be affected by highly active lipases in human milk.

Aims: Free fatty acid receptor 4 (Ffar4) is a G-protein-coupled receptor for endogenous medium-/long-chain fatty acids that attenuates metabolic disease and inflammation. However, the function of Ffar4 in the heart is unclear. Given its putative beneficial role, we hypothesized that Ffar4 would protect the heart from pathologic stress., Methods and Results: In mice lacking Ffar4 (Ffar4KO), we found that Ffar4 is required for an adaptive response to pressure overload induced by transverse aortic constriction (TAC), identifying a novel cardioprotective function for Ffar4. Following TAC, remodelling was worsened in Ffar4KO hearts, with greater hypertrophy and contractile dysfunction. Transcriptome analysis 3-day post-TAC identified transcriptional deficits in genes associated with cytoplasmic phospholipase A2α signalling and oxylipin synthesis and the reduction of oxidative stress in Ffar4KO myocytes. In cultured adult cardiac myocytes, Ffar4 induced the production of the eicosapentaenoic acid (EPA)-derived, pro-resolving oxylipin 18-hydroxyeicosapentaenoic acid (18-HEPE). Furthermore, the activation of Ffar4 attenuated cardiac myocyte death from oxidative stress, while 18-HEPE rescued Ffar4KO myocytes. Systemically, Ffar4 maintained pro-resolving oxylipins and attenuated autoxidation basally, and increased pro-inflammatory and pro-resolving oxylipins, including 18-HEPE, in high-density lipoproteins post-TAC. In humans, Ffar4 expression decreased in heart failure, while the signalling-deficient Ffar4 R270H polymorphism correlated with eccentric remodelling in a large clinical cohort paralleling changes observed in Ffar4KO mice post-TAC., Conclusion: Our data indicate that Ffar4 in cardiac myocytes responds to endogenous fatty acids, reducing oxidative injury, and protecting the heart from pathologic stress, with significant translational implications for targeting Ffar4 in cardiovascular disease., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Background: Regulation of the endoplasmic reticulum (ER) stress pathway is critical to mammary epithelial cell function throughout pregnancy, lactation, and involution. Treatment with trans -10, cis -12 conjugated linoleic acid (t10c12CLA) suppresses mammary lipogenesis and stimulates the ER stress pathway. The ER stress pathway includes tribbles pseudokinase 3 (TRB3), a protein that regulates cellular energy and insulin signaling., Objectives: Our objective was to describe the effect of TRB3 deficiency on milk fat synthesis and determine if TRB3 deficiency protects against suppression of mammary lipogenesis., Methods: First, mammary Trb3 expression was observed throughout pregnancy and lactation using ancillary microarray data ( n  = 4/time point). Second, intake, litter growth, and milk clot fatty acid (FA) profile of Trb3 knockout (KO) C57BL/6N mice were compared with wild-type (WT) and heterozygous (HET) mice throughout first ( n  ≥ 8/group) and second ( n  ≥ 6/group) lactation. Lastly, the interaction between Trb3 genotype and 2 treatments that suppress mammary lipogenesis, t10c12CLA and high safflower oil (HO) diet, was investigated in a 2 × 2 factorial design ( n  ≥ 6/group)., Results: Trb3 expression was higher during late pregnancy and lactation. Trb3 KO and HET mice had lower feed intake, dam weight, and litter growth throughout first, but not second, lactation than WT mice. Treatment with t10c12CLA decreased litter growth (28%; P  < 0.0001) and feed intake (8%; P  < 0.0001) regardless of Trb3 genotype. When fed the HO diet, Trb3 KO mice had 17% higher mammary de novo synthesized FAs (<16 carbons; P int  = 0.002) than WT mice. Mammary ER stress and lipogenic genes were mostly unaltered by Trb3 deficiency., Conclusions: Overall, TRB3 plays a minor role in regulating mammary lipogenesis, because Trb3 deficiency had only a limited protective effect against diet-induced suppression of lipogenesis., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Methods to increase the amount of omega-3 (n-3) PUFAs in milk are desirable for neonatal health. The n-3 PUFA, α-linolenic acid (18:3n-3), can be elongated to EPA (20:5n-3) and DHA (22:6n-3). n-6 PUFAs suppress tissue n-3 PUFA incorporation, but the effect of SFAs is not clear., Objectives: In this study, we compared the effects of SFAs and n-6 PUFAs on n-3 PUFA incorporation into milk and tissues of lactating mice and tissues of their offspring., Methods: Female CD-1 mice were bred at 8 wk of age. All experimental diets included 3% flaxseed oil and were begun on day 8 of lactation: low-fat diet (LFD); high-SFA diet (SAT), with an additional 12% saturated oil; or high-linoleic-acid diet (HLA), with 12% high-linoleic-acid oil (% kcal, carbohydrates:fat:protein: LFD, 49:24:27; both SAT and HLA, 35:46:19; n = 5/treatment). After 5 d, pup stomach milk clot FA profiles, tissue FA profiles in dams and pups, and mammary and hepatic expression of lipid metabolism genes in dams were analyzed. Data were analyzed by ANOVA with treatment diet as a fixed effect., Results: Dams in all groups had similar total milk fat concentrations, but both SAT and HLA decreased the concentration of n-3 PUFAs (SAT: -23%; HLA: -31%) compared with LFD, and HLA increased milk n-6 FAs by 347% compared with SAT. SAT pups had n-3 PUFA tissue concentrations similar to LFD, but HLA pups had lower n-3 PUFAs than SAT pups in multiple tissues (liver, -32%; kidney, -29%; heart, -28%; muscle, -18%). Mammary expression of lipid metabolism genes was mostly unchanged, but hepatic expression of elongases and desaturases was decreased with SAT compared with LFD [elongation of very-long-chain fatty acid (Elov)5, -42%; Elov6, -64%; fatty acid desaturase (Fads)1, -33%; Fads2, -44%]., Conclusions: HLA decreased n-3 PUFA concentrations across multiple pup tissues compared with SAT. This suggests that high dietary n-6 PUFAs suppress n-3 PUFA incorporation in neonates., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Oxylipins are metabolites of polyunsaturated fatty acids that mediate cardiovascular health by attenuation of inflammation, vascular tone, hemostasis, and thrombosis. Very low-density lipoproteins (VLDL) contain oxylipins, but it is unknown whether the liver regulates their concentrations. In this study, we used a perfused liver model to observe the effect of inflammatory lipopolysaccharide (LPS) challenge and soluble epoxide hydrolase inhibition (sEHi) on VLDL oxylipins. A compartmental model of deuterium-labeled linoleic acid and palmitic acid incorporation into VLDL was also developed to assess the dependence of VLDL oxylipins on fatty acid incorporation rates. LPS decreased the total fatty acid VLDL content by 30% [6%,47%], and decreased final concentration of several oxylipins by a similar amount (13-HOTrE, 35% [4%,55%], -1.3 nM; 9(10)-EpODE, 29% [3%,49%], -2.0 nM; 15(16)-EpODE, 29% [2%,49%], -1.6 nM; AA-derived diols, 32% [5%,52%], -2.4 nM; 19(20)-DiHDPA, 31% [7%,50%], -1.0 nM). However, the EPA-derived epoxide, 17(18)-EpETE, was decreased by 75% [49%,88%], (-0.52 nM) with LPS, double the suppression of other oxylipins. sEHi increased final concentration of DHA epoxide, 16(17)-EpDPE, by 99% [35%,193%], (2.0 nM). Final VLDL-oxylipin concentrations with LPS treatment were not correlated with linoleic acid kinetics, suggesting they were independently regulated under inflammatory conditions. We conclude that the liver regulates oxylipin incorporation into VLDL, and the oxylipin content is altered by LPS challenge and by inhibition of the epoxide hydrolase pathway. This provides evidence for delivery of systemic oxylipin signals by VLDL transport., (© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

In adipose, insulin functions to suppress intracellular lipolysis and secretion of nonesterified fatty acid (NEFA) into plasma. We applied glucose and NEFA minimal models (MM) following a frequently sampled intravenous glucose tolerance test (FSIVGTT) to assess glucose-specific and NEFA-specific insulin resistance. We used total NEFA and individual fatty acids in the NEFA MM, comparing the model parameters in metabolic syndrome (MetSyn) subjects ( n = 52) with optimally healthy controls (OptHC; n = 14). Results are reported as mean difference (95% confidence interval). Using the glucose MM, MetSyn subjects had lower [-73% (-82, -57)] sensitivity to insulin (S i ) and higher [138% (44, 293)] acute insulin response to glucose (AIR g ). Using the NEFA MM, MetSyn subjects had lower [-24% (-35, -13)] percent suppression, higher [32% (15, 52)] threshold glucose (g s ), and a higher [81% (12, 192)] affinity constant altering NEFA secretion (ϕ). Comparing fatty acids, percent suppression was lower in myristic acid (MA) than in all other fatty acids, and the stearic acid (SA) response was so unique that it did not fit the NEFA MM. MA and SA percent of total were increased at 50 min after glucose injection, whereas oleic acid (OA) and palmitic acid (PA) were decreased ( P < 0.05). We conclude that the NEFA MM, as well as the response of individual NEFA fatty acids after a FSIVGTT, differ between OptHC and MetSyn subjects and that the NEFA MM parameters differ between individual fatty acids.

Background: Supplemental long-chain omega-3 (n-3) fatty acids (EPA and DHA) raise erythrocyte EPA + DHA [omega-3 index (O3I)] concentrations, but the magnitude or variability of this effect is unclear., Objective: The purpose of this study was to model the effects of supplemental EPA + DHA on the O3I., Methods: Deidentified data from 1422 individuals from 14 published n-3 intervention trials were included. Variables considered included dose, baseline O3I, sex, age, weight, height, chemical form [ethyl ester (EE) compared with triglyceride (TG)], and duration of treatment. The O3I was measured by the same method in all included studies. Variables were selected by stepwise regression using the Bayesian information criterion., Results: Individuals supplemented with EPA + DHA (n = 846) took a mean ± SD of 1983 ± 1297 mg/d, and the placebo controls (n = 576) took none. The mean duration of supplementation was 13.6 ± 6.0 wk. The O3I increased from 4.9% ± 1.7% to 8.1% ± 2.7% in the supplemented individuals ( P < 0.0001). The final model included dose, baseline O3I, and chemical formulation type (EE or TG), and these explained 62% of the variance in response (P < 0.0001). The model predicted that the final O3I (and 95% CI) for a population like this, with a baseline concentration of 4.9%, given 850 mg/d of EPA + DHA EE would be ∼6.5% (95% CI: 6.3%, 6.7%). Gram for gram, TG-based supplements increased the O3I by about 1 percentage point more than EE products., Conclusions: Of the factors tested, only baseline O3I, dose, and chemical formulation were significant predictors of O3I response to supplementation. The model developed here can be used by researchers to help estimate the O3I response to a given EPA + DHA dose and chemical form., (Copyright © American Society for Nutrition 2019.)

Objective: Diets rich in fermentable fibres provide an array of health benefits; however, many patients with IBD report poor tolerance to fermentable fibre-rich foods. Intervention studies with dietary fibres in murine models of colonic inflammation have yielded conflicting results on whether fibres ameliorate or exacerbate IBD. Herein, we examined how replacing the insoluble fibre, cellulose, with the fermentable fibres, inulin or pectin, impacted murine colitis resulting from immune dysregulation via inhibition of interleukin (IL)-10 signalling and/or innate immune deficiency ( Tlr5 KO)., Design: Mice were fed with diet containing either cellulose, inulin or pectin and subjected to weekly injections of an IL-10 receptor (αIL-10R) neutralising antibody. Colitis development was examined by serological, biochemical, histological and immunological parameters., Results: Inulin potentiated the severity of αIL10R-induced colitis, while pectin ameliorated the disease. Such exacerbation of colitis following inulin feeding was associated with enrichment of butyrate-producing bacteria and elevated levels of caecal butyrate. Blockade of butyrate production by either metronidazole or hops β-acids ameliorated colitis severity in inulin-fed mice, whereas augmenting caecal butyrate via tributyrin increased colitis severity in cellulose containing diet-fed mice. Elevated butyrate levels were associated with increased IL-1β activity, while inhibition of the NOD-like receptor protein 3 by genetic, pharmacologic or dietary means markedly reduced colitis., Conclusion: These results not only support the notion that fermentable fibres have the potential to ameliorate colitis but also caution that, in some contexts, prebiotic fibres can lead to gut dysbiosis and surfeit colonic butyrate that might exacerbate IBD., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Oxylipins are lipid mediators produced from polyunsaturated fatty acid (PUFA) metabolism, and are thought to be a molecular explanation for the diverse biological effects of PUFAs. Like PUFAs, oxylipins are distinguished by their omega-6 (n6) or omega-3 (n3) chemistry. We review the use of n6 oxylipins as biomarkers of disease and their use in diagnosis and risk assessment. We show cases where oxylipins derived from linoleate (LA) or arachidonate (AA) produced by the activities of lipoxygenase, cyclooxygenase, epoxygenase, ω/ω-1 hydroxylase, and autooxidation are useful as biomarkers or risk markers. HODEs, KODEs, EpOMEs, DiHOMEs, and other metabolites of LA as well as prostanoids, HETEs, KETEs, EpETrEs, and DiHETrEs, and other metabolites of AA were useful for understanding the different signaling environments in conditions from traumatic brain injury, to major coronary events, dyslipidemia, sepsis, and more. We next evaluate interventions that alter the concentrations of n6 oxylipins in plasma. We note the utility and response of each plasma fraction, and the generally increasing utility from the non-esterified, to the esterified, to the lipoprotein fractions. Finally, we review the effects which are specifically related to n6 oxylipins and most likely to be beneficial. Both n6 and n3 oxylipins work together in an exceedingly complex matrix to produce physiological effects. This overview should provide future investigators with important perspectives for the emerging utility of n6 oxylipins as products of n6 PUFAs in human health., (Copyright © 2018. Published by Elsevier Ltd.)

Military personnel engage in strenuous physical activity and load carriage. This study evaluated the role of body mass and of added mass on aerobic performance (uphill treadmill exercise) and pulmonary function. Performance on a traditional unloaded run test (4.8 km) was compared with performance on loaded tasks. Subjects performed an outdoor 4.8-km run and 4 maximal treadmill tests wearing loads of 0, 10, 20, and 30 kg. Subjects' pulmonary function (forced expired volume in 1 second [FEV1], forced vital capacity [FVC], and maximal voluntary ventilation [MVV]) was tested with each load, and peak values of heart rate, oxygen consumption ((Equation is included in full-text article.)), ventilation (VE), and respiratory exchange ratio (RER) were measured during each treadmill test. Performance on the 4.8-km run was correlated with treadmill performance, measured as time to exhaustion (TTE), with the strength of the correlation decreasing with load (r = 0.87 for 0 kg to 0.76 for 30 kg). Body mass was not correlated with TTE, other than among men with the 30-kg load (r = 0.48). During treadmill exercise, all peak responses other than RER decreased with load. Pulmonary function measures (FEV1, FVC, and MVV) decreased with load. Body mass was poorly correlated with treadmill performance, but added mass decreased performance. The decreased performance may be in part because of decreased pulmonary function. Unloaded 4.8-km run performance was correlated to unloaded uphill treadmill performance, but less so as load increased. Therefore, traditional run tests may not be an effective means of evaluating aerobic performance for military field operations.