•n6 oxylipins have use in predicting risk, particularly for cardiovascular disease.•Esterified n6 oxylipins appear to be more sensitive to dietary and pharmaceutical interventions, particularly among ...HDL, LDL, and VLDL.•Numerous n6 oxylipins have activities that complement n3 oxylipins. In some cases, n6 oxylipins have activities that counter-act detrimental activities of n3 oxylipins.
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.
Arguably, the most striking geochemical distinction between Earth and the Moon has been the virtual lack of water (hydrogen) in the latter. This conclusion was recently challenged on the basis of ...geochemical data from lunar materials that suggest that the Moon's water content might be far higher than previously believed. We measured the chlorine isotope composition of Apollo basalts and glasses and found that the range of isotopic values from -1 to +24 per mil (per thousand) versus standard mean ocean chloride is 25 times the range for Earth. The huge isotopic spread is explained by volatilization of metal halides during basalt eruption--a process that could only occur if the Moon had hydrogen concentrations lower than those of Earth by a factor of approximately 10⁴ to 10⁵, implying that the lunar interior is essentially anhydrous.
In cross-sectional studies and short-term clinical trials, it has been suggested that there is a positive dose-response relation between alcohol consumption and HDL concentrations. However, ...prospective data have been limited.
We sought to determine the association between total alcohol intake, the type of alcohol-containing beverage, and the 6-y (2006-2012) longitudinal change in HDL-cholesterol concentrations in a community-based cohort.
A total of 71,379 Chinese adults (mean age: 50 y) who were free of cardiovascular diseases and cancer and did not use cholesterol-lowering agents during follow-up were included in the study. Alcohol intake was assessed via a questionnaire in 2006 (baseline), and participants were classified into the following categories of alcohol consumption: never, past, light (women: 0-0.4 servings/d; men: 0-0.9 servings/d), moderate (women: 0.5-1.0 servings/d; men: 1-2 servings/d), and heavy (women: >1.0 servings/d; men: >2 servings/d). HDL-cholesterol concentrations were measured in 2006, 2008, 2010, and 2012. We used generalized estimating equation models to examine the associations between baseline alcohol intake and the change in HDL-cholesterol concentrations with adjustment for age, sex, smoking, physical activity, obesity, hypertension, diabetes, liver function, and C-reactive protein concentrations.
An umbrella-shaped association was observed between total alcohol consumption and changes in HDL-cholesterol concentrations. Compared with never drinkers, past, light, moderate, and heavy drinkers experienced slower decreases in HDL cholesterol of 0.012 mmol · L
· y
(95% CI: 0.008, 0.016 mmol · L
· y
), 0.013 mmol · L
· y
(95% CI: 0.010, 0.016 mmol · L
· y
), 0.017 mmol · L
· y
(95% CI: 0.009, 0.025 mmol · L
· y
), and 0.008 mmol · L
· y
(95% CI: 0.005, 0.011 mmol · L
· y
), respectively (
< 0.0001 for all), after adjustment for potential confounders. Moderate alcohol consumption was associated with the slowest increase in total-cholesterol:HDL-cholesterol and triglyceride:HDL-cholesterol ratios. We observed a similar association between hard-liquor consumption and the HDL-cholesterol change. In contrast, greater beer consumption was associated with slower HDL-cholesterol decreases in a dose-response manner.
Moderate alcohol consumption was associated with slower HDL-cholesterol decreases; however, the type of alcoholic beverage had differential effects on the change in the HDL-cholesterol concentration.
The gut microbiota plays a key role in host metabolism. Toll-like receptor 5 (TLR5), a flagellin receptor, is required for gut microbiota homeostasis. Accordingly, TLR5-deficient (T5KO) mice are ...prone to develop microbiota-dependent metabolic syndrome. Here we observed that T5KO mice display elevated neutral lipids with a compositional increase of oleate C18:1 (n9) relative to wild-type littermates. Increased oleate contribution to hepatic lipids and liver SCD1 expression were both microbiota dependent. Analysis of short-chain fatty acids (SCFAs) and 13C-acetate label incorporation revealed elevated SCFA in ceca and hepatic portal blood and increased liver de novo lipogenesis in T5KO mice. Dietary SCFAs further aggravated metabolic syndrome in T5KO mice. Deletion of hepatic SCD1 not only prevented hepatic neutral lipid oleate enrichment but also ameliorated metabolic syndrome in T5KO mice. Collectively, these results underscore the key role of the gut microbiota-liver axis in the pathogenesis of metabolic diseases.
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•T5KO mice microbiota generates more cecal SCFA, substrates for hepatic lipogenesis•Dietary SCFA aggravate metabolic syndrome in T5KO mice•Hepatic SCD1 plays a key role in the development of metabolic syndrome in T5KO mice•Metabolic syndrome in T5KO mice is microbiota-liver axis dependent
Singh et al. identify a gut microbiota-liver axis responsible for the metabolic syndrome developed by TLR5-deficient mice and show that short-chain fatty acids generated by gut bacterial fermentation of dietary fiber fuel SCD1-mediated lipogenesis in the liver, which promotes insulin resistance and inflammation.
Abstract Heart failure (HF) affects 5.7 million in the U.S., and despite well-established pharmacologic therapy, the 5-year mortality rate remains near 50%. Furthermore, the mortality rate for HF has ...not declined in years, highlighting the need for new therapeutic options. Omega-3 polyunsaturated fatty acids (ω3-PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are important regulators of cardiovascular health. However, questions of efficacy and mechanism of action have made the use of ω3-PUFAs in all cardiovascular disease (CVD) controversial. Here, we review recent studies in animal models of HF indicating that ω3-PUFAs, particularly EPA, are cardioprotective, with the results indicating a threshold for efficacy. We also examine clinical studies suggesting that ω3-PUFAs improve outcomes in patients with HF. Due to the relatively small number of clinical studies of ω3-PUFAs in HF, we discuss EPA concentration-dependency on outcomes in clinical trials of CVD to gain insight into the perceived questionable efficacy of ω3-PUFAs clinically, with the results again indicating a threshold for efficacy. Ultimately, we suggest that the main failing of ω3-PUFAs in clinical trials might be a failure to reach a therapeutically effective concentration. We also examine mechanistic studies suggesting that ω3-PUFAs signal through free fatty acid receptor 4 (Ffar4), a G-protein coupled receptor (GPR) for long-chain fatty acids (FA), thereby identifying an entirely novel mechanism of action for ω3-PUFA mediated cardioprotection. Finally, based on mechanistic animal studies suggesting that EPA prevents interstitial fibrosis and diastolic dysfunction, we speculate about a potential benefit for EPA-Ffar4 signaling in heart failure preserved with ejection fraction.
Multiple intelligences (MI) theory was one of the first modern theories of intelligence to be based on neural evidence. The relationship between creativity and intelligence has been a matter of ...debate as has the role of MI theory in gifted education. An extensive array of neuroscience evidence is reviewed as it pertains to the validity of MI theory. Data are presented that describe neural architectures for a proposed new category of Cognitive Qualities that includes Creative Cognition, Esthetic Judgement, and Insight/Intuition. The implications for understanding the minds of gifted individuals with the goal of personalizing instruction to maximize achievement and life development are reviewed. Five key principles drawn from educational cognitive neuroscience are proposed as guidelines for using MI theory to enhance instruction and inspire curriculum design to account for the unique cognitive qualities of gifted and talented individuals.
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