Scope
Long‐chain (LC)‐PUFAs act as precursors for the special class of retinal lipids known as very‐long‐chain (VLC)‐PUFAs and the effect of diabetes on retinal VLC‐PUFA levels is unexplored. In ...order to understand the supplemental effect of omega‐3 (n‐3) LC‐PUFAs on decreasing levels of VLC‐PUFAs due to diabetes, Nile rats, which develop diabetes spontaneously, and Akita mouse, a genetic diabetes model, are chosen.
Methods and results
Human retinal punches from donors are collected from an eye bank; lipids are extracted and analyzed to study the alterations in VLC‐PUFAs and their omega‐3/omega‐6 (n‐3/n‐6) ratios. Nile rats are fed a high‐fat diet to induce hyperglycemia, and then an n‐3 PUFA‐rich diet is fed to the experimental group for 2 months. Diabetic male Akita mice and WT mice are fed with 5% fish‐oil mixed in with their chow for 2 months to observe the effect of n‐3 PUFAs. Results indicate that VLC‐PUFA levels are lower in human diabetic and retinopathic retinal punches compared to age‐matched controls. With supplementation of n‐3 PUFAs, there is a significant increase in n‐3/n‐6 VLC‐PUFA ratios in both animal models compared to diabetic controls.
Conclusion
Dietary supplementation with n‐3 LC‐PUFAs helps to prevent progression of diabetes and associated retinopathy.
VLC‐PUFAs are a special class of non‐dietary fatty acids present in the vertebrate retina and testes. Diabetic animal models are used to observe the effect of n‐3 LC‐PUFAs on replenishing VLC‐PUFAs and it is observed that n‐3 PUFAs not only help to improve n‐3 VLC‐PUFAs but also decrease blood glucose levels and improve diabetic conditions in these animal models.
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An 8-week feeding trial with black seabream, Acanthopagrus schlegelii, was conducted to evaluate effects of dietary n-3 LC-PUFA/n-6 C18 PUFA (LC-PUFA, long-chain polyunsaturated fatty acid; C18 PUFA, ...PUFA with 18 atoms of carbon) ratio on growth, feed utilization, fatty acid composition and lipid related gene expression. Five isoproteic and isolipidic diets were formulated to contain different n-3 LC-PUFA/n-6 C18 PUFA ratios: 0.1, 0.4, 0.5, 0.8, 1.0. Each diet was assigned randomly to feed triplicate net cage of 90 fish (30 fish per net cage) of initial weight 3.0 ± 0.0 g. As a result, final weight (FW), weight gain (WG), specific growth rate (SGR), feed efficiency (FE) and protein efficiency ratio (PER) were all significantly affected by dietary n-3 LC-PUFA/n-6 C18 PUFA ratio (P < 0.05). Fish fed the diet with a n-3 LC-PUFA/n-6 C18 PUFA ratio of 0.8 showed the highest FW, WG, SGR, FE, PER. There was no significant differences in survival rate (SR), hepatosomatic index (HIS), viscerosomatic index (VIS), intraperitoneal fat ratio (IPF) among all treatments (P > 0.05). Likewise,The moisture contents, crude protein, crude lipid and ash contents in the whole body and muscle were all not affected by experimental diets (P > 0.05). Tissue fatty acid profiles reflected the diets. The highest concentration of triacylglycerol (TG) was observed in fish fed the lowest ratio (0.1) (P < 0.05). However,the highest activities of alanine aminotransferase (ALT) and aspartate transaminase (AST) as well as the highest content of cholesterol (CHOL) were all found in fish fed the diet containing n-3 LC-PUFA/n-6 C18 PUFA ratio of 1.0 (P < 0.05). Hepatic G6pd, Lpl and Hsl activities were significantly affected by dietary n-3 LC-PUFA/n-6 C18 PUFA ratio (P < 0.05). Similarly, the expression levels of fas, accɑ, g6pd, cpt1ɑ and atgl were influenced significantly among treatments, the highest fas, accɑ, g6pd, cpt1ɑ and atgl expression levels were obtained in fish fed the lowest dietary n-3 LC-PUFA/n-6 C18 PUFA ratio of 0.1 (P < 0.05). In conclusion, according to quadratic regression analysis, the optimum dietary n-3 LC-PUFA/n-6 C18 PUFA ratio was 0.7 for juvenile black seabream to obtain the maximum growth. Moreover, this study also indicated that dietary n-3 LC-PUFA/n-6 C18 PUFA ratio affected fatty acid profiles and significantly influenced lipid metabolism.
•The optimum dietary n-3 LC-PUFA/n-6 C18 PUFA is 0.7 for juvenile black seabream to obtain the maximum growth•High ratio of n-3 LC-PUFA/n-6 C18 PUFA could cause hepatocytes or their cell membranes injury.•Dietary n-3 LC-PUFA/n-6 C18 PUFA ratio could significantly impact tissue fatty acid profiles, hematological characteristics.•Expression of lipid related genes as well as activities of some hepatic metabolic enzymes were significantly regulated by different dietary n-3 LC-PUFA/n-6 C18 PUFA ratios.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Oxylipins are bioactive lipids formed by the monooxygenation of polyunsaturated fatty acids (PUFA). Eicosanoids derived from arachidonic acid (ARA) are the most well‐studied class of oxylipins that ...influence brain functions in normal health and in disease. However, comprehensive profiling of brain oxylipins from other PUFA with differing functions, and the examination of the effects of dietary PUFA and sex differences in oxylipins are warranted. Therefore, female and male Sprague–Dawley rats were provided standard rodent diets that provided additional levels of the individual n‐3 PUFA α‐linolenic acid (ALA), eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), or the n‐6 PUFA linoleic acid (LNA) alone or with ALA (LNA + ALA) compared to essential fatty acid‐sufficient control diets. Oxylipins and PUFA were quantified in whole brains using HPLC‐MS/MS and GC, respectively. Eighty‐seven oxylipins were present at quantifiable levels: 51% and 17% of these were derived from ARA and DHA, respectively. At the mass level, ARA and DHA oxylipins comprised 81–90% and 6–12% of total oxylipins, while phospholipid ARA and DHA represented 25–35% and 49–62% of PUFA mass, respectively. Increasing dietary n‐3 PUFA resulted in higher levels of oxylipins derived from their precursor PUFA; otherwise, the brain oxylipin profile was largely resistant to modulation by diet. Approximately 25% of oxylipins were higher in males, and this was largely unaffected by diet, further revealing a tight regulation of brain oxylipin levels. These fundamental data on brain oxylipin composition, diet effects, and sex differences will help guide future studies examining the functions of oxylipins in the brain.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Multiple sclerosis (MS) is a neurologic autoimmune disease, which is the leading cause of nontraumatic neurologic disability in young adults in United States and Europe. n‐3 polyunsaturated fatty ...acids (PUFA) are reported to mitigate severity of this disease. Recent studies suggest that phospholipid (PL) form of dietary n‐3 PUFA may lead to their higher tissue accretion than triacylglycerol (TAG) form. We compared efficacy of PL‐docosahexaenoic acid (22:6n‐3) (DHA) and TAG‐DHA on onset and severity of experimental autoimmune encephalomyelitis (EAE) in a mouse model of MS. Female mice were fed low alpha‐linolenic acid (18:3n‐3) (ALA) diet (control) for 2 weeks and then fed either control, 0.3%, or 1.0% DHA (PL or TAG) for 4 weeks pre‐EAE induction and 4 weeks post‐EAE induction. The brain and spinal cord n‐6:n‐3 ratio was significantly lower in all mice fed DHA compared to control. EAE onset was delayed in mice fed both DHA forms and concentrations, except for 1% TAG‐DHA. The inverse association between the EAE score and the brain DHA concentration was nonsignificant at the end of the study (p = 0.08). Daily EAE scores of mice fed different DHA diets did not differ from control, however, the score of all DHA groups combined during days 9–16 was lower (p = 0.028) compared to the control. During days 17–22, the EAE score trended lower in 0.3% TAG‐DHA and during days 23–28, the EAE score trended lower in both PL‐DHA groups than those in all other groups. These findings suggest that TAG‐DHA may be more effective than PL‐DHA in the early phases of EAE, and in the final outcome, PL‐DHA may be more effective than TAG‐DHA.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background Identifying possible influencing factors is crucial for the depression symptoms of women experiencing infertility. This study aims to explore the association between polyunsaturated fatty ...acids (PUFAs) and the odds of depression symptoms in women experiencing infertility. Methods This is a cross-sectional study based on the National Health and Nutrition Examination Survey (NHANES). PUFA intake was obtained through a 24-h dietary recall interview. Depression symptoms were defined using the Patient Health Questionnaire-9 (PHQ-9) with a score of ≥10 points or as taking antidepressants. The association between PUFA and depression was assessed using a logistic regression model by calculating the odds ratio (OR) with 95% confidence interval (CI). Subgroup analysis was carried out based on menopausal status and female hormone use. Results There were 725 participants included for analysis. After adjusting the covariables, lower odds of depression symptoms were found in patients with the intake of omega-3 PUFA (OR = 0.48, 95% CI: 0.24–0.96) and omega-6 PUFA (OR = 0.24, 95% CI: 0.14–0.42) in the second tertile (T2) in comparison to the first tertile (T1). The intake of α-linolenic (ALA) (OR = 0.48, 95% CI: 0.23–0.97) and linoleic acid (OR = 0.24, 95% CI: 0.14–0.41) in T2 was also found to be related to the reduced odds of depression symptoms in comparison to T1. Conclusions Our findings suggest a potential association between moderate omega-3 and omega-6 PUFA intake and a reduced risk of depression symptoms in women experiencing infertility. This implies that clinicians might find it useful to consider dietary advice that includes PUFA-rich foods as part of a broader strategy to address mental health in this patient group. However, further research is needed to confirm these preliminary findings and to establish the optimal levels of PUFA intake for mental health benefits.
As the largest secondary lymphoid organ, the spleen plays an important role in immune responses. The role of arachidonic acid (ARA) and its 20‐carbon eicosanoids in modulating immune function has ...long been of interest. However, recent advances have enabled the identification of numerous other n‐6 and n‐3 polyunsaturated fatty acid (PUFA)‐derived oxylipins. Here, we investigate the effects of diet and sex on the spleen nonesterified oxylipin profiles and phospholipid and neutral lipid PUFA composition in Sprague–Dawley rats supplemented with oils rich in α‐linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or linoleic acid. Dietary ALA, EPA, and DHA resulted in lower levels of ARA and ARA oxylipins. Oxylipins derived from other n‐6 PUFA were also reduced despite no or opposite effect on their PUFA levels. Each diet also resulted in higher levels of oxylipins almost exclusively derived from the supplemented PUFA, despite PUFA in the same biosynthetic pathway also often being increased. Further, while oxylipin differences often reflected changes to phospholipid PUFA, there were instances where they corresponded more closely to changes in neutral lipid PUFA. With respect to sex effects, >50% of lipoxygenase ARA‐derived oxylipins were higher in males in at least one diet group, while multiple DHA oxylipins were lower in males only in rats provided the DHA diet. This fundamental description of oxylipin composition in the spleen, including the influence of diet and sex and the relationship to PUFA composition, will help inform future studies examining the functions of these oxylipins under physiological and pathological conditions.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Recent studies suggest that dietary krill oil leads to higher omega‐3 polyunsaturated fatty acids (n‐3 PUFA) tissue accretion compared to fish oil because the former is rich in n‐3 PUFA esterified as ...phospholipids (PL), while n‐3 PUFA in fish oil are primarily esterified as triacylglycerols (TAG). Tissue accretion of the same dietary concentrations of PL‐ and TAG‐docosahexaenoic acid (22:6n‐3) (DHA) has not been compared and was the focus of this study. Mice (n = 12/group) were fed either a control diet or one of six DHA (1%, 2%, or 4%) as PL‐DHA or TAG‐DHA diets for 4 weeks. Compared with the control, DHA concentration in liver, adipose tissue (AT), heart, and eye, but not brain, were significantly higher in mice consuming either PL‐ or TAG‐DHA, but there was no difference in DHA concentration in all tissues between the PL‐ or TAG‐DHA forms. Consumption of PL‐ and TAG‐DHA at all concentrations significantly elevated eicosapentaenoic acid (20:5n‐3) (EPA) in all tissues when compared with the control group, while docoshexapentaenoic acid (22:5n‐6) (DPA) was significantly higher in all tissues except for the eye and heart. Both DHA forms lowered total omega‐6 polyunsaturated fatty acids (n‐6 PUFA) in all tissues and total monounsaturated fatty acids (MUFA) in the liver and AT; total saturated fatty acid (SFA) were lowered in the liver but elevated in the AT. An increase in the DHA dose, independent of DHA forms, significantly lowered n‐6 PUFA and significantly elevated n‐3 PUFA concentration in all tissues. Our results do not support the claim that the PL form of n‐3 PUFA leads to higher n‐3 PUFA tissue accretion than their TAG form.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
•Inappropriate intakes of n-6 and n-3 fatty acids in pregnancy carry risks for the fetal development and diseases in later life.•In addition to deficit intakes of several dietary factors by mothers ...in India, n-3 deficiency seems to be the most prominent.•The n-3 deficiency affects fetal growing tissues globally such as the brain, motor nerve, muscle, eye, adiposity etc.•Maternal deficiency of n-3 fatty acids may also affect placental angiogenesis and thereby its structure and function.•Maternal intake of n-3 fatty acids must be followed with ISSFAL guidelines to improve maternal health and fetal development.
Polyunsaturated fatty acids (PUFAs) play multiple physiological roles. They regulate the structure and function of cell membranes and cell growth and proliferation, and apoptosis. In addition, PUFAs are involved in cellular signaling, gene expression and serve as precursors to second messengers such as eicosanoids, docosanoids etc. and regulate several physiological processes including placentation, inflammation, immunity, angiogenesis, platelet function, synaptic plasticity, neurogenesis, bone formation, energy homeostasis, pain sensitivity, stress, and cognitive functions. Linoleic acid, 18:2n-6 (LA) and alpha-linolenic acid, 18:3n-3 (ALA) are the two essential fatty acids obtained from the diets and subsequently their long-chain polyunsaturated fatty acids (LCPUFAs) are accumulated in the body. The maternal plasma LCPUFAs especially accumulated in larger amounts in the brain during the third trimester of pregnancy via the placenta and postnatally from mother's breast milk. Various studies, including ours, suggest PUFA's important role in placentation, as well as in growth and development of the offspring. However, intakes of maternal n-3 PUFAs during pregnancy and lactation are much lower in India compared with the Western population. In India, n-3 fatty acid status is further reduced by higher intake of n-6 PUFA rich oils and trans fats. More data on the impacts of long term maternal n-3 PUFA deficiency on placental structure and function, gene expression, epigenetic changes and resultant cognitive function of fetus & infants are emerging. This review summarizes the impacts of n-3 PUFA deficiency in utero on fetal growth and development, adiposity, energy metabolism, musculoskeletal development, and epigenetic changes in feto-placental axis from the recently available pre-clinical and clinical data.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The impact of fat intake on hypercholesterolemia and related atherosclerotic cardiovascular diseases has been studied for decades. However, the current evidence base suggests that fatty acids also ...influences cardiometabolic diseases through other mechanisms including effects on glucose metabolism, body fat distribution, blood pressure, inflammation, and heart rate. Furthermore, studies evaluating single fatty acids have challenged the simplistic view of shared health effects within fatty acid groups categorized by degree of saturation. In addition, investigations of endogenous fatty acid metabolism, including genetic studies of fatty acid metabolizing enzymes, and the identification of novel metabolically derived fatty acids have further increased the complexity of fatty acids’ health impacts. This Special Issue aims to include original research and up-to-date reviews on genetic and dietary modulation of fatty acids, and the role and function of dietary and metabolically derived fatty acids in cardiometabolic health.
Practitioners of ancient societies from the time of Hippocrates and earlier recognized and treated the signs of inflammation, heat, redness, swelling, and pain with agents that block or inhibit ...proinflammatory chemical mediators. More selective drugs are available today, but this therapeutic concept has not changed. Because the acute inflammatory response is host protective to contain foreign invaders, much of today's pharmacopeia can cause serious unwanted side effects, such as immune suppression. Uncontrolled inflammation is now considered path‐ophysiologic and is associated with many widely occurring diseases such as cardiovascular disease, neurodegen‐erative diseases, diabetes, obesity, and asthma, as well as classic inflammatory diseases (e.g., arthritis and periodontal diseases). The inflammatory response, when self‐limited, produces a superfamily of chemical media‐tors that stimulate resolution of the response. Specialized proresolving mediators (SPMs), identified in recent years, are endogenous mediators that include the n‐3–derived families resolvins, protectins, and maresins, as well as arachidonic acid–derived (n‐6) lipoxins, which promote resolution of inflammation, clearance of microbes, reduction of pain, and promotion of tissue regeneration via novel mechanisms. Aspirin and statins have a positive impact on these resolution pathways, producing epimeric forms of specific SPMs, whereas other drugs can disrupt timely resolution. In this article, evidence from recent human and preclinical animal studies is reviewed, indicating that SPMs are physiologic mediators and pharmacologic agonists that stimulate resolution of inflammation and infection. The findings suggest that it is time to challenge current treatment practices—namely, using inhibitors and antagonists alone—and to develop immunoresolvents as agonists to test resolution pharmacology and their role in catabasis for their therapeutic potential. —Serhan, C. N. Treating inflammation and infection in the 21st century: new hints from decoding resolution mediators and mechanisms. FASEB J. 31, 1273–1288 (2017) www.fasebj.org
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