Rat Brain Fatty Acids In Essential Fatty Acid Deficiency

Brain lipid composition was studied in rats depleted in essential fatty acids (EFA) from birth through one year, as well as in rats depleted for various periods up to 90 days and then refed EFA. Brain EFA were reduced in the depleted animals. Refeeding with EFA restored brain EFA pattern, brain weight, and body weight to normal. Thus, the fatty acid composition of brain con be altered by diet even in relatively mature rats.     

Nutrition in Brain Development and Aging: Role of Essential Fatty Acids

The essential fatty acids (EFAs), particularly the n-3 long-chain polyunsaturated fatty acids (LCPs), are important for brain development during both the fetal and postnatal period. They are also increasingly seen to be of value in limiting the cognitive decline during aging. EFA deficiency was first shown over 75 years ago, but the more subtle effects of the n-3 fatty acids in terms of skin changes, a poor response to linoleic acid supplementation, abnormal visual function, and peripheral neuropathy were only discovered later. Both n-3 and n-6 LCPs play important roles in neuronal growth, development of synaptic processing of neural cell interaction, and expression of genes regulating cell differentiation and growth. The fetus and placenta are dependent on maternal EFA supply for their growth and development, with docosahexaenomic acid (DHA)-supplemented infants showing significantly greater mental and psychomotor development scores (breast-fed children do even better). Dietary DHA is needed for the optimum functional maturation of the retina and visual cortex, with visual acuity and mental development seemingly improved by extra DHA. Aging is also associated with decreased brain levels of DHA: fish consumption is associated with decreased risk of dementia and Alzheimer's disease, and the reported daily use of fish-oil supplements has been linked to improved cognitive function scores, but confirmation of these effects is needed.     

Dietary n-3 and n-6 Fatty Acids Alter Avian Pituitary Sensitivity

Abstract

The effects of dietary saturated and polyunsaturated fatty acids (PUFAs) of the n-3 and n-6 series on avian pituitary sensitivity were investigated by infusing human growth hormone (GH) releasing hormone--fragment 1-29--and chicken luteinising hormone releasing hormone (LHRH) into catheterized broiler chickens. At 3 weeks of age three groups (n=18; six birds per group) were fed for 6 weeks isonitrogenous and isoenergetic experimental diets containing 80 g/kg of edible tallow (saturated fatty acids), fish oil (n-3 PUFAs) or sunflower oil (n-6 PUFAs). Jugular catheterisation was performed under general anaesthesia during week four of the dietary treatments and the birds allowed 7 days post surgery to recover. A bolus of LHRH (20 μg/bird) and a GH releasing hormone (12.5 μg/kg) infusion was given on different days to each chicken and serial blood samples taken over a 1 h period. Plasma luteinising hormone and GH concentrations were measured by radioimmunoassay. Pre-infusion GH concentrations were similar for the tallow, fish and sunflower oil dietary groups (5.2±3.9, 5.2±1.0 and 6.1±3.1 ng/ml, respectively), however, GH concentration in response to the GH releasing hormone infusion was elevated in the sunflower oil group (44.7±5.7 ng/ml) when compared to chicken fed tallow (33.7±9.7 ng/ml) or fish oil (21.3±5.0 ng/ml). There was a significant decrease (P<0.05) in the clearance rate of plasma GH for the birds fed the fish oil compared with those fed sunflower oil with an intermediate value being observed in the tallow fed group. Pre-infusion plasma luteinising hormone concentrations for the birds fed tallow (3.2±0.7 ng/ml) were significantly elevated (P<0.05) when compared to birds fed either the sunflower oil (0.84±0.25 ng/ml) or fish oil (0.93±0.22 ng/ml) diets. There were no significant differences between the dietary groups in either the maximal plasma luteinising concentration or its disappearance rate following the LHRH infusion. The data demonstrate that dietary fatty acids alter avian pituitary sensitivity and this modulation is determined by the nature of the dietary fat rather than the degree of saturation per se. In addition, this study also shows that dietary fats have a differential effect on pituitary cell activity and are specific to certain pituitary cell types.     

The Role of n-3 Polyunsaturated Fatty Acids in the Prevention and Treatment of Breast Cancer

Breast cancer (BC) is the most common cancer among women worldwide. Dietary fatty acids, especially n-3 polyunsaturated fatty acids (PUFA), are believed to play a role in reducing BC risk. Evidence has shown that fish consumption or intake of long-chain n-3 PUFA, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are beneficial for inhibiting mammary carcinogenesis. The evidence regarding α-linolenic acid (ALA), however, remains equivocal. It is essential to clarify the relation between ALA and cancer since ALA is the principal source of n-3 PUFA in the Western diet and the conversion of ALA to EPA and DHA is not efficient in humans. In addition, the specific anticancer roles of individual n-3 PUFA, alone, have not yet been identified. Therefore, the present review evaluates ALA, EPA and DHA consumed individually as well as in n-3 PUFA mixtures. Also, their role in the prevention of BC and potential anticancer mechanisms of action are examined. Overall, this review suggests that each n-3 PUFA has promising anticancer effects and warrants further research.     

Consequences of Essential Fatty Acids

Essential fatty acids (EFA) are nutrients that form an amazingly large array of bioactive mediators that act on a large family of selective receptors. Nearly every cell and tissue in the human body expresses at least one of these receptors, allowing EFA-based signaling to influence nearly every aspect of human physiology. In this way, the health consequences of specific gene-environment interactions with these nutrients are more extensive than often recognized. The metabolic transformations have similar competitive dynamics for the n-3 and n-6 homologs when converting dietary EFA from the external environment of foods into the highly unsaturated fatty acid (HUFA) esters that accumulate in the internal environment of cells and tissues. In contrast, the formation and action of bioactive mediators during tissue responses to stimuli tend to selectively create more intense consequences for n-6 than n-3 homologs. Both n-3 and n-6 nutrients have beneficial actions, but many common health disorders are undesired consequences of excessive actions of tissue n-6 HUFA which are preventable. This review considers the possibility of preventing imbalances in dietary n-3 and n-6 nutrients with informed voluntary food choices. That action may prevent the unintended consequences that come from eating imbalanced diets which support excessive chronic actions of n-6 mediators that harm human health. The consequences from preventing n-3 and n-6 nutrient imbalances on a nationwide scale may be very large, and they need careful evaluation and implementation to avoid further harmful consequences for the national economy.     

A Systemic Review of the Roles of n-3 Fatty Acids in Health and Disease

Attention to the role of n-3 long-chain fatty acids in human health and disease has been continuously increased during recent decades. Many clinical and epidemiologic studies have shown positive roles for n-3 fatty acids in infant development; cancer; cardiovascular diseases; and more recently, in various mental illnesses, including depression, attention-deficit hyperactivity disorder, and dementia. These fatty acids are known to have pleiotropic effects, including effects against inflammation, platelet aggregation, hypertension, and hyperlipidemia. These beneficial effects may be mediated through several distinct mechanisms, including alterations in cell membrane composition and function, gene expression, or eicosanoid production. A number of authorities have recently recommended increases in intakes of n-3 fatty acids by the general population. To comply with this recommendation a variety of food products, most notably eggs, yogurt, milk, and spreads have been enriched with these fatty acids. Ongoing research will further determine the tissue distribution, biological effects, cost-effectiveness, and consumer acceptability of such enriched products. Furthermore, additional controlled clinical trials are needed to document whether long-term consumption or supplementation with eicosapentaenoic acid/docosahexaenoic acid or the plant-derived counterpart (α-linolenic acid) results in better quality of life.     

A Consistency Model for Identifying the Effects of n-3 and n-6 Fatty Acids on Lipoproteins in Dialysis Patients

Numerous randomized controlled trials (RCTs) and meta-analyses have assessed the effects of supplemental dietary polyunsaturated fatty acids (PUFAs) on levels of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) and the LDL/HDL ratio in patients receiving renal replacement therapy (RRT). However, results are ambiguous due to mixed reports of various nutrients used in the intervention group. We performed a network meta-analysis of RCTs to assess the effects of PUFAs on lipid profiles in patients undergoing RRT. RCTs performed before November 2021 were gathered from three databases. The means, standard deviations and the number of cases for each arm were independently extracted by two authors to form a network meta-analysis of LDL and HDL levels and the LDL/HDL ratio in a random effects model. Twenty-eight RCTs (n = 2017 subjects) were included in this study. The pooled results revealed that the combination of omega-3 fatty acids (n-3) and omega-6 fatty acids (n-6) produced significantly lower LDL (standardized mean difference (SMD) = −1.43, 95% confidence interval: −2.28 to −0.57) than the placebo. Both n-3 fatty acids (SMD = 0.78) and the combination of n-3 + n-6 (SMD = 1.09) benefited HDL significantly compared with placebo. Moreover, n-3 alone also exhibited a significantly lower LDL/HDL ratio than placebo. Collectively, PUFAs seem to be adequate nutrients for controlling lipoproteins in patients undergoing RRT. Specifically, n-3 + n-6 supplementation improved LDL levels, while n-3 improved HDL levels and the LDL/HDL ratio. However, our data provide limited information on specific dosages of PUFAs to form a concrete recommendation.     

(n-3) Fatty Acids: Clinical Trials in People with Type 2 Diabetes

Recent human clinical trials of the effects of (n-3) fatty acids on participants with type 2 diabetes (T2D) were reviewed, focusing on 11 clinical trials conducted within the past 4 y, and subsequent to a Cochrane Database meta-analysis of this topic. Doses of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in these studies were mostly in the range of ～2 g/d provided for 6 wk to 6 mo. Summarizing across these studies, there were no changes in fasting glucose or insulin compared with baseline or placebo. (n-3) Fatty acids generally decreased serum triglycerides but had varying effects on serum cholesterol, LDL cholesterol, and HDL cholesterol. A few studies indicated beneficial effects of (n-3) fatty acids on arterial blood flow. The effects of EPA and/or DHA have not yet been studied in clinical trials in participants at risk for T2D; the prevention or exacerbation of T2D by fish oil or EPA and DHA supplements of amounts >0.5 g/d deserves study. The prevention of adverse vascular effects of T2D by (n-3) fatty acids may be a promising direction for further study.     

Intake of Fish and n-3 Fatty Acids and Future Risk of Metabolic Syndrome

Background

Whether or not fish and n-3 fatty acid intake is associated with the metabolic syndrome risk has not been carefully evaluated. This study investigated the effect of fish and n-3 fatty acid intake on the incidence of metabolic syndrome and on the individual risk factors for the syndrome.

Methods

A population-based prospective cohort study included 3,504 male and female Koreans aged 40 to 69 years from the Korean Genome Epidemiology Study. At the beginning of follow-up, all individuals were free of metabolic syndrome and known cardiovascular disease. Each participant completed a food frequency questionnaire. Incident cases of metabolic syndrome were identified by biennial health examinations during a follow-up period between April 17, 2003, and November 17, 2006. Pooled logistic regression analysis was applied to obtain an odds ratio (OR) of metabolic syndrome with its 95% confidence interval (CI) for fish or n-3 fatty acid intake.

Results

After controlling for potential cardiovascular risk factors, multivariate OR for metabolic syndrome was 0.43 (95% CI 0.23 to 0.83) for men who ate fish daily when compared with those eating fish less than once a week. Similarly, metabolic syndrome risk was halved for men in the top decile of n-3 fatty acid intake when compared with those in the bottom decile (OR 0.53, 95% CI 0.28 to 0.99). In particular, fish intake was significantly associated with triglyceride level and high-density lipoprotein cholesterol level among the metabolic syndrome components. For women, apparent associations were not observed between fish intake or n-3 fatty acid intake and metabolic syndrome risk.

Conclusions

In a prospective study, high consumption of fish and n-3 fatty acids was significantly associated with a lower risk of metabolic syndrome among men, but not among women. Whether or not encouraging fish intake can help prevent the development of metabolic syndrome warrants further studies.     

n-6/n-3脂肪酸配方油对大鼠血脂和脂质过氧化的影响

目的研究不同脂肪酸n-6/n-3组成的配方油对大鼠血脂和脂质过氧化的影响.方法成年SD雄性大鼠喂饲含相同胆固醇(0.5%,W/W)、饱和脂肪酸(占供给能量10%)、单不饱和脂肪酸(占供给能量13%)和多不饱和脂肪酸(占供给能量12%),但不同脂肪酸n-6/n-3比(6.48、2.07、0.93、031)的4种配方油的高脂合成饲料60天,观察大鼠血脂及脂质过氧化的变化.结果4种配方油比猪油均显著降低血清总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、LDL-C/HDL-C、AI[(TC-HDL-C/HDL-C,致动脉粥样硬化指数)],升高HDL-C/TC;配方油D具有独特的升高血清HDL-C2的作用;配方油A、C、D显著降低血清TG,而配方油B作用不明显.以n-3多不饱和脂肪酸占优势的配方油C、D比以n-6多不饱和脂肪酸占优势的配方油A、B显著地升高血清丙二醛,降低血清超氧化物歧化酶、全血谷胱甘肽过氧化物酶活性.4组配方油大鼠的心、脑脂褐质含量均比实验前增高,各配方油间无显著差异;心、脑脂褐质与血脂的相关分析发现心、脑脂褐质与血清TC、LDL-C呈正相关,与血清高密度脂蛋白胆固醇(HDL-C)、甘油三酯(TG)关系不明显.结论从预防动脉粥样硬化的角度,脂肪酸n-6/n-3比在2.07～6.48范围内是合理的脂肪酸供给模式.     

Enhanced Absorption of n-3 Fatty Acids from Emulsified Compared with Encapsulated Fish Oil

Health benefits of n-3 fatty acids are well-established. However, consumption of adequate dietary sources of these fatty acids is inadequate. Oral fish oil supplements are an alternative means of consuming adequate long-chain n-3 fatty acids in individuals who do not consume sufficient dietary sources. However, palatability can present a problem with compliance. Emulsifying fish oil allows for production of a pleasant-tasting supplement and can enhance digestion and absorption of the fatty acids. We investigated the rate and extent of absorption of emulsified fish oil compared with capsular triglyceride fish oil supplements in humans. Participants subjectively rated palatability of these products. A randomized, crossover-designed, open-label trial was performed in which 10 healthy volunteers received emulsified fish oil and capsular triglyceride fish oil orally. Blood samples were collected at 0, 2, 4, 8, 24, and 48 hours to determine the absorption of individual fatty acids into plasma phospholipid fatty acids. At the completion of blood collection, subjects were asked to subjectively rate the tolerance and acceptability of the two supplements. During a 48-hour period, there was enhanced absorption of total n-3 and eicosapentaenoic acid (0.67%±0.16%, 0.45%±0.06%; P<0.01; 0.34%±0.05%, 0.23%±0.04%; P=0.05; emulsified fish oil and capsular triglyceride fish oil, respectively) observed for the emulsified fish oil treatment. Our findings indicate that a single dose of emulsified fish oil resulted in enhanced absorption of total n-3 eicosapentaenoic acid and docosahexaenoic acid as evidenced by changes in phospholipid fatty acids composition compared with the capsular triglyceride fish oil during the 48-hour observation period. Both supplements were subjectively rated and found to be well-tolerated by participants.     

足月新生儿血浆和红细胞膜必需脂肪酸水平的动态观察

目的 了解不同喂养方式对足月新生儿期内必需脂肪酸水平的影响.方法 用毛细管气相色谱法测定了38例足用新生儿出生时脐血和生后第7天、14天、28天静脉血血浆和红细胞膜必需脂肪酸水平.结果 生后 14天、28天母乳喂养儿静脉血血浆花生四烯酸、廿二碳六烯酸水平显著高于人工喂养儿.亚油酸、亚麻酸水平两组间无显著差异.结论 人工喂养可引起足月新生儿必需脂肪酸缺乏,应提供合理奶方,大力提倡母乳喂养.     

n-3 Polyunsaturated Fatty Acids and Mechanisms to Mitigate Inflammatory Paracrine Signaling in Obesity-Associated Breast Cancer

Globally, the prevalence of obesity is increasing which subsequently increases the risk of the development of obesity-related chronic diseases. Low-grade chronic inflammation and dysregulated adipose tissue inflammatory mediator/adipokine secretion are well-established in obesity, and these factors increase the risk of developing inflammation-associated cancer. Breast cancer is of particular interest given that increased inflammation within the subcutaneous mammary adipose tissue depot can alter the local tissue inflammatory microenvironment such that it resembles that of obese visceral adipose tissue. Therefore, in obese women with breast cancer, increased inflammatory mediators both locally and systemically can perpetuate inflammation-associated pro-carcinogenic signaling pathways, thereby increasing disease severity. Herein, we discuss some of these inflammation-associated pro-carcinogenic mechanisms of the combined obese breast cancer phenotype and offer evidence that dietary long chain n-3 polyunsaturated fatty acids (PUFA) may have utility in mitigating the severity of obesity-associated inflammation and breast cancer.     

Causal Effects of Serum Levels of n-3 or n-6 Polyunsaturated Fatty Acids on Coronary Artery Disease: Mendelian Randomization Study

We aimed to investigate the causal effects of n-3 and n-6 polyunsaturated fatty acids (PUFAs) on the risk of coronary artery disease (CAD) through Mendelian randomization (MR) analysis. This MR study utilized a genetic instrument developed from previous genome-wide association studies for various serum n-3 and n-6 PUFA levels. First, we calculated the allele scores for genetic predisposition of PUFAs in individuals of European ancestry in the UK Biobank data (N = 337,129). The allele score-based MR was obtained by regressing the allele scores to CAD risks. Second, summary-level MR was performed with the CARDIoGRAMplusC4D data for CAD (N = 184,305). Higher genetically predicted eicosapentaenoic acid and dihomo-gamma-linolenic acid levels were significantly associated with a lower risk of CAD both in the allele-score-based and summary-level MR analyses. Higher allele scores for linoleic acid level were significantly associated with lower CAD risks, and in the summary-level MR, the causal estimates by the pleiotropy-robust MR methods also indicated that higher linoleic acid levels cause a lower risk of CAD. Arachidonic acid showed significant causal estimates for a higher risk of CAD. This study supports the causal effects of certain n-3 and n-6 PUFA types on the risk of CAD.