Total dietary fat and fatty acid content modifies plasma phospholipid fatty acids,desaturase activity indices,and urinary prostaglandin E in women

Compared with diets high in fat, low-fat diets are associated with reduced risk of cardiovascular disease. We hypothesized that a low-fat (LF) (20% fat) and an LF high–omega-3 (n-3) fatty acid diet (LFn3) (23% fat with 3% as α-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid [DHA]) would enhance n-3 composition of plasma phospholipid fatty acid and reduce urinary prostaglandin E₂ (PGE₂) relative to a high-fat diet (HF) (40% fat) and that these changes would be associated with alterations in δ5 desaturase (D5D) and δ6 desaturase (D6D) activity. Phospholipid fatty acids and urinary PGE₂ were measured, and D5D and D6D activity indices calculated in a crossover trial in 17 postmenopausal women fed each of 3 test diets (HF, LF, and LFn3) for 8-week feeding periods. Desaturase activity indices were calculated as D5D, 20:4n-6/20:3n-6, and D6D, 20:3n-6/18:2n-6. Plasma phospholipid fatty acid, α-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid (DPA), DHA, and total n-3 fatty acids increased, whereas linoleic acid and arachidonic acid decreased with consumption of LFn3. The LF resulted in enhanced arachidonic acid and DHA. High fat reduced D6D, whereas both HF and LF increased D5D. Urinary PGE₂ was reduced in response to both the LF and LFn3 diets. Low-fat diets, with or without long-chain n-3 fatty acids, promote positive health effects due in part to favorable alteration of plasma phospholipid fatty acid profiles and modification in desaturase activity indices, suggesting that the type and amount of fat consumed are modifiable risk factors for the prevention of cardiovascular disease.     

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.     

Dietary n-3 polyunsaturated fatty acids alter lipid composition and decrease prostaglandin synthesis in rat spleen

Three groups of rats were fed a semisynthetic diet containing 10% olive oil, 10% corn oil, or 10% menhaden oil for three weeks. Olive oil was used as a control and corn and menhaden oils as sources of n-6 and n-3 fatty acids, respectively. The spleen phospholipids were enriched with eicosapentaenoic (20:5 n-3) and docosahexaenoic acids (22:6 n-3) in rats on menhaden oil diets. The enrichment of these n-3 fatty acids was accompanied by a decrease in the arachidonic acid content (20:4 n-6) of spleen phospholipids. The syntheses of prostaglandin E₂ (PGE₂), 6-keto prostaglandin F_1α (6 keto PGF_1α) and thromboxane B₂ (TXB₂) from endogenous substrates in n-3 fatty acid enriched spleens were decreased by 50, 57 and 80% respectively. These studies indicate that dietary n-3 fatty acids can effectively displace arachidonic acid from phospholipids and decrease prostaglandin synthesis in rat spleen.     

Anti-inflammatory and anti-angiogenic effect of long chain n-3 polyunsaturated fatty acids in intestinal microvascular endothelium

Background & aims

The role of endothelial cells in inflammatory bowel disease has been recently emphasized. Endothelial activation and expression of adhesion molecules are critical for leukocytes recruitment into the inflammatory wall. Compelling evidence demonstrated anti-inflammatory effects of long chain n-3 PUFA in inflammatory models. We previously showed that long chain n-3 PUFA (EPA and DHA) inhibited inflammatory response in epithelial and dendritic cells. As long chain n-3 PUFA treatment led to a decreased expression of adhesion molecules in endothelial cells from other organs, we have now investigated their effect on intestinal endothelial cells in vitro and in colitic rats.

Methods

In vitro study: Primary culture of human intestinal microvascular endothelial cells (HIMEC) were pre-treated with DHA and then incubated with IL-1β. In vivo study: Colitis was induced in 2 groups at day0 by intrarectal injection of 2-4-6-trinitrobenzen sulfonic acid (TNBS). Rats received by gavage either fish oil, rich in EPA and DHA (TNBS+n-3) or an isocaloric isolipidic oil formula for 14 days.

Results

DHA led to a decreased VCAM-1, TLR4, cyclooxygenase-2 and VEGFR2 expression and a decreased production of IL-6, IL-8 and GM-CSF and a reduced production of PGE₂ and LTB₄ (p < 0.001) in IL-1β-induced HIMEC. Similarly, dietary intervention with fish oil rich in EPA and DHA significantly decreased colon production of PGE₂ and LTB_4, endothelial VCAM-1 and VEGFR2 in rats with colitis.

Conclusions

Data obtained from in vitro and in vivo studies reveal a potential anti-angiogenic role of long chain n-3 PUFA in intestinal endothelial cells. This protective effect of long chain n-3 PUFA may partly explain the observed benefit of dietary intake of long chain n-3 PUFA in IBD development.     

不同比例n-6/n-3多不饱和脂肪酸对小鼠良性前列腺增生和炎性细胞因子的影响

目的比较不同比例n-6/n-3PUFAs对小鼠良性前列腺增生(benign prostatic hyperplasia,BPH)和免疫功能的影响。方法采用油菜花粉二氧化碳超临界萃取物调节小鼠饲料中n-6/n-3PUFAs的比值。小鼠随机分为正常对照组(A组)、前列腺增生模型组(B组)、n-6/n-3PUFAs=1.7组(C组)、n-6/n-3PUFAs=5组(D组)、n-6/n-3PUFAs=10组(E组)和非那雄胺治疗组(F组)共6组。测定炎性细胞因子、双氢睾酮(dihydrotestosterone,DHT)含量及增生的形态学变化。结果 C组和D组可显著降低前列腺增生指数(P0.01),降低前列腺酸性磷酸酶(prostatic acid phosphatase,PACP)的活性(P0.01),生长状况明显好于模型组;实验组均能降低促炎症细胞因子TNF-α、IL-1β和IL-6的含量,D组降幅最明显。前列腺组织切片观察D组增生减退明显,腺腔内仅有少量淡红色分泌物。C组显著降低血清中DHT含量(P0.01)。结论油菜花粉萃取物调节饲料n-6/n-3PUFAs的比值可以明显降低BPH临床症状及病理学指标,n-6/n-3PUFAs=5时具有最显著的效果,其可能的作用机制与抑制炎症发生有关。     

Dietary eicosapentaenoic acid normalizes hippocampal omega-3 and 6 polyunsaturated fatty acid profile,attenuates glial activation and regulates BDNF function in a rodent model of neuroinflammation induced by central interleukin-1β administration

Purpose

Interleukin (IL)-1β can activate glial cells to trigger neuroinflammation and neurodegeneration. Lower omega (n)-3 polyunsaturated fatty acids (PUFAs) and lower n-3/n-6 PUFA ratios occur in the brain of patients with Alzheimer’s disease (AD). We have previously reported that an n-3 PUFA, eicosapentaenoic acid (EPA), can improve memory and attenuate neurodegeneration-like changes in animal models of AD. However, whether and how EPA modulates glial cell activity and functions remains unclear. The aim of this study was to test the hypothesis that EPA may attenuate neuroinflammation by inhibiting microglial activation and microglia-produced proinflammatory cytokines, and by enhancing the expression of astrocytes-produced neurotrophins and their receptors.

Methods

Male Long-Evans rats were fed either palm oil supplemented diet or EPA supplemented diet for 42 days. On day 36 of diet feeding, rats received an intracerebroventricular injection of IL-1β or saline for 7 days. The glial activation, the expression of amyloid precursor protein (APP), calcium-dependent phospholipase (cPL) A2, brain-derived neurotrophic factor (BDNF) and its receptor, and PUFA profile in the hippocampus were analyzed.

Results

IL-1β elevated biomarkers of microglial CD11b and astrocyte GFAP expression, increased the expression of APP, tumor-necrosis factor (TNF)-α, but reduced BDNF and its receptor (TrKB). IL-1β also lowered n-3 EPA and docosapentaenoic acid concentrations but increased n-6 PUFAs and cPLA2 activity in the hippocampus. EPA supplement normalized the n-3 and n-6 PUFA profiles and cPLA2 levels, inhibited glial activation, reduced APP and TNF-α expression, as well as up-regulated BDNF and TrKB.

Conclusion

Supplementation with EPA appear to have potential effects on improving glial over-activation, n3/n6 imbalance and BDNF down-regulation, which contribute to anti-inflammatory and may provide beneficial effects on inflammation-associated disease such as AD.

     

孕期及哺乳期n-6/n-3脂肪酸变化对仔鼠脑源性神经营养因子基因表达的影响

目的 探讨孕期及哺乳期n-3 多不饱和脂肪酸(n-3 polyunsaturated fatty acids,n-3 PUFAs)摄入量及其与n-6 PUFAs比例对仔鼠脑源性神经营养因子(brain-derived neurotrophic factor,bdnf)基因表达的影响。方法 使用6~8周龄清洁级C57BL/6J雌性小鼠,随机分为5 组,分别给予n-3 PUFAs缺乏和4种不同含量n-3 PUFAs(n-6/n-3 PUFAs比值分别为15∶1、5∶1、1∶1及1∶5)饲料喂养。小鼠12~14周龄时雌雄合笼交配繁殖,仔鼠断乳后继续行母鼠相同饲料喂养,分别在生后7 d、21 d和3 月时被处死后取脑。同时,分别从n-3 PUFAs缺乏组和n-6/n-3 PUFAs(5∶1)组中选取等量仔鼠,21 d断乳后相互交换饲料喂养至3个月,处死后取脑。采用实时荧光定量PCR技术测定脑皮质bdnf基因mRNA的表达。结果 与n-3 PUFAs缺乏饲料组相比,对于7 d和21 d幼年仔鼠,只有n-6/n-3 PUFAs(1∶5)饲料组bdnf基因mRNA表达量显著升高;对于3 月龄成年仔鼠,各含n-3 PUFAs饲料组bdnf基因mRNA的表达均升高。对于孕期和哺乳期n-3 PUFAs缺乏饲料组仔鼠,断乳后给予含n-3 PUFAs饲料喂养未能提升脑皮质bdnf基因mRNA表达;而孕期和哺乳期含n-3 PUFAs饲料喂养的仔鼠,断乳后给予n-3 PUFAs缺乏饲料喂养时,脑皮质bdnf基因mRNA表达量见一定程度的升高。结论 孕期及哺乳期可能需要较高的n-3 PUFAs摄入,才能满足幼年期诱导脑bdnf表达之需。保证生命早期n-3 PUFAs的适量摄入,有助于维持成年期bdnf的正常表达。     

Moderate Freshwater Fish Intake,but Not n-3 Polyunsaturated Fatty Acids,Is Associated with a Reduced Risk of Small for Gestational Age in a Prospective Cohort of Chinese Pregnant Women

BackgroundAlthough previous studies have found that maternal fish intake is associated with fetal growth, the role of freshwater fish intake remains unknown.ObjectiveOur aim was to examine the relationships of freshwater fish and n-3 polyunsaturated fatty acids (PUFAs) intake with the risk of small for gestational age (SGA) in Chinese pregnant women.DesignThis was a prospective analysis of data from the Tongji Birth cohort in Wuhan, China, from 2018 to 2021.Participants/settingsThis study included 1,701 pregnant women who had completed a food frequency questionnaire dietary assessment during mid-pregnancy.Main outcome measuresIntake of fish was assessed by a semi-quantitative food frequency questionnaire. Total intake of n-3 PUFAs was the sum of data collected from both dietary and supplemental sources of n-3 PUFAs. Birth information was extracted from medical records.Statistical analysesMultivariate logistic regression models were applied to estimate odds ratios and 95% CIs.ResultsThe median (interquartile range) intake of freshwater fish and total n-3 PUFAs was 12.1 (4.3 to 26.4) g/d and 68.2 (24.5 to 370.0) mg/d, respectively. Moderate intake of freshwater fish was associated with reduced risk of SGA. Compared with the lowest quintile (0–3.2 g/d), the multivariable-adjusted odds ratio for women in the fourth quintile of freshwater fish intake (17.9 to 30.0 g/d) was 0.50 (95% CI 0.25 to 0.96). We found a nonlinear association between freshwater fish intake and SGA risk (P_nonlinearity = .027). However, maternal n-3 PUFAs intake was not significantly associated with SGA risk, either from total intake or from dietary sources alone.ConclusionsModerate freshwater fish intake during pregnancy is associated with lower risk of SGA in a Chinese population. This finding provides supportive evidence for freshwater fish intake during pregnancy, particularly for the inland areas of developing countries.     

Proportions of Polyunsaturated Fatty Acids in Umbilical Cord Blood at Birth Are Related to Atopic Eczema Development in the First Year of Life

Atopic eczema, the most common atopic disease in infants, may pave the way for sensitization and allergy later in childhood. Fatty acids have immune-regulating properties and may regulate skin permeability. Here we examine whether the proportions of fatty acids among the infant and maternal plasma phospholipids at birth were associated with maternal dietary intake during pregnancy and development of atopic eczema during the first year of age in the Nutritional impact on Immunological maturation during Childhood in relation to the Environment (NICE) birth cohort. Dietary data were collected with a semi-quantitative food frequency questionnaire, fatty acids were measured with GC-MS and atopic eczema was diagnosed by a pediatric allergologist at 12 months of age. We found that higher proportions of n-6 PUFAs (including arachidonic acid) but lower proportions of n-3 PUFAs (including DPA) in the infant’s phospholipids at birth were associated with an increased risk of atopic eczema at 12 months of age. The n-6 and n-3 PUFAs were related to maternal intake of meat and fish, respectively. Our results suggest that prenatal exposure to unsaturated fatty acids is associated with eczema development in the infant. Maternal diet during pregnancy may partly explain the fatty acid profiles in utero.     

Docosahexaenoic acid and eicosapentaenoic acid affect ovarian prostaglandin levels differently in rats

Prostaglandins (PGs) play a key role in the regulation of ovulation. Typically, ingestion of the long-chain n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) has been found to decrease, whereas arachidonic acid (ARA) increases PG biosynthesis in most systems. We hypothesized that DHA and EPA would decrease ovarian PGE₂, enhancing ovulation, with combined EPA and DHA having the greatest effect, whereas ARA would increase PGE₂, suppressing ovulation. Our objective was to determine how 0.3-g/100-g diet DHA and EPA alone or combined, or ARA would affect tissue composition, ovulation, and PG synthesis in rats. After 27 days on diet and ovulation induction, ovaries were isolated and analyzed from 22 pups per diet. Eicosapentaenoic acid alone reduced ovarian n-6 PUFA attributable to reduced ARA incorporation. Arachidonic acid ingestion reduced and EPA enhanced ovarian n-3 PUFA to levels above what was seen with DHA or DHA/EPA combinations. Docosahexaenoic acid alone increased total PGE 1.5-fold over control, whereas neither differed from the remaining treatments. Increased total PGE with DHA was attributable to elevated PGE₃ with PGE₂ unchanged by diet, and PGE₃ only increased with DHA ingestion alone. Total PGF differed from control with the highest DHA intake, alone or combined with EPA, or with ARA ingestion (P < .05). Increased PGF with DHA was attributable to increased PGF_3α. Experimental diets did not alter ovulation from control. Results indicate that DHA and EPA consumption at human achievable doses differently alters ovarian phospholipids and PGs associated with ovulation with potential for significant 3-series PG without significantly perturbing ovulation.     

Prepubertal ethanol exposure alters hypothalamic transforming growth factor-α and erbB1 receptor signaling in the female rat

Glial-derived transforming growth factor alpha (TGFα) activates the erbB1/erbB2 receptor complex on adjacent glial cells in the medial basal hypothalamus (MBH). This receptor activation stimulates the synthesis and release of prostaglandin-E₂ (PGE₂) from the glial cells, which then induces the release of prepubertal luteinizing hormone-releasing hormone (LHRH) secretion from nearby nerve terminals; thus, showing the importance of glial-neuronal communications at the time of puberty. Ethanol (EtOH) is known to cause depressed prepubertal LHRH secretion and delayed pubertal development. In this study, we assessed whether short-term EtOH exposure could alter the hypothalamic glial to glial signaling components involved in prepubertal PGE₂ secretion. Immature female rats began receiving control or EtOH diets beginning when 27 days old. The animals were killed by decapitation after 4 and 6 days of treatment and confirmed to be in the late juvenile stage of development. Blood and brain tissues were collected for gene, protein, and hormonal assessments. Real-time polymerase chain reaction (PCR) analysis demonstrated that EtOH did not affect basal levels of erbB1 gene expression in the MBH. Expression of total erbB1 protein was also unaffected; however, the EtOH caused suppressed phosphorylation of erbB1 protein in the MBH at both 4 and 6 days (P < .01) as revealed by Western blotting. Phosphorylation and total protein levels of erbB2 receptor were not affected by EtOH exposure. Because this receptor is critical for PGE₂ synthesis/release, which mediates the secretion of LHRH, we assessed whether in vivo EtOH exposure could affect the release of PGE₂. EtOH exposure for 6 days suppressed (P < .01) basal levels of PGE₂ released into the medium. The effects of 4- and 6-day EtOH exposure on gene and protein expressions of TGFα, an upstream component in the activation of erbB1/erbB2, were also studied. The levels of TGFα mRNA were increased markedly at 4 days (P < .001), but declined to near basal levels by 6 days in the EtOH-treated animals. The EtOH caused increases in TGFα protein expression at both 4 (P < .001) and 6 (P < .01) days; hence, suggesting that the EtOH inhibited release of the peptide. We confirmed this inhibition by showing decreased (P < .01) TGFα released from MBHs incubated in vitro following 6 days of EtOH exposure in vivo. Thus, these results demonstrate that EtOH is capable of interfering with hypothalamic glial to glial signaling processes involved in prepubertal PGE₂ secretion.     

The Associations of Erythrocyte Fatty Acids with Whole Blood Mineral Elements in Children

Background. Minerals play important biological roles in lipid metabolism. The primary aim of this study was to examine the relationships between erythrocyte fatty acids (FAs) levels with whole blood mineral elements concentrations among Chinese children. Methods. A cross-sectional study was conducted. A total of 435 children aged 4–7 years were recruited. Whole blood mineral elements were determined by atomic absorption spectrometry and erythrocyte FAs composition by gas chromatography-mass spectrometer. Results. There were direct correlations between Zn and C18:2n-6 (FDR corrected p = 0.019), total n-6 PUFAs (FDR corrected p = 0.034), and total PUFAs (FDR corrected p = 0.034). Direct correlations were found between whole blood Zn and C18:1n-9 (FDR corrected p = 0.035), C24:1n-9 (FDR corrected p = 0.023), total MUFAs (FDR corrected p = 0.023), and C18:2n-6 (FDR corrected p = 0.048) in the Cu < P50 group. In the Cu ≥ P50 group, Mg was inversely related to most FAs (All FDR corrected p < 0.05). In the Zn < P50 group, Cu was directly related to C24:1n-9, total MUFAs, C20:5n-3, C22:6n-3, total n-3 PUFAs, C20:4n-6, total n-6 PUFAs, total PUFAs, and total FAs (All FDR corrected p < 0.05). Conclusions. Whole blood Cu and Zn levels were directly linked to several FAs levels in the erythrocytes of children. The interactions of Mg, Cu, and Zn with fatty acids may affect FA metabolism, in which Mg influences FA absorption.     

Dietary omega-3 fatty acids differentially influence ova release and ovarian cyclooxygenase-1 and cyclooxygenase-2 expression in rats

Ovulation is a prostaglandin (PG)-dependent process. Although n-3 polyunsaturated fatty acids (PUFA) and conjugated linoleic acid (CLA) have differing effects in the body, both reduce PG synthesis. We hypothesized that dietary n-3 fatty acids and CLA would differentially alter ovarian PG profiles through reductions in expression of enzymes involved in PG biosynthesis resulting in enhanced ovulation. Our objectives were to determine how dietary stearidonic acid and eicosapentaenoic acid (EPA) at 0.3 g/100 g diet and mixed isomers of CLA at 0.7 g/100 g diet, human achievable levels with daily consumption of fish or beef and dairy products, respectively, would influence ovulation and ovarian cyclooxygenase-1 (COX-1) and COX-2 expression in ovulation-induced rats. After 27 days on diet and ovulation induction, ovaries were isolated and analyzed from 22 pups per diet. Eicosapentaenoic acid ingestion reduced ova release by 16% while increasing PGE₂ and PGF_2α release without altering COX-1 or COX-2 expression. Conversely, ovarian COX-1 expression was increased 135% with stearidonic acid ingestion associated with increased PGF_2α without altering PGE₂ or ova release. Conjugated linoleic acid ingestion reduced COX-2 expression to 65% of that in rats consuming control and EPA diets; however, without affecting ovulation or PGs. Although it is generally believed that the COX-2 is the primary COX involved in ovulation, these results demonstrated that the n-3 PUFA differently affect ovarian COX-1 expression and that this effect differs from CLA, which reduced COX-2 expression. Further, although ovarian PGF_2α is the primary PG altered by dietary n-3 PUFA, n-3 PUFA differentially influence ovarian PG biosynthesis and can decrease ova release, possibly induced through constitutive COX-1 enzyme expression.     

Association Between Serum Long-Chain n-3 and n-6 Polyunsaturated Fatty Acid Profiles and Glomerular Filtration Rate Assessed by Serum Creatinine and Cystatin C Levels in Japanese Community-Dwellers

Background

Plasma concentration of n-3 polyunsaturated fatty acids (PUFAs) has been reported to be associated with renal function in Western populations. However, few studies have investigated the association between serum long-chain n-3 and n-6 PUFA profiles and renal function in a Japanese population with high marine-derived long-chain n-3 PUFA intake.

Methods

A cross-sectional study was performed in 549 Japanese rural community-dwellers aged 40 to 64 years. In adjusted analysis of covariance, we assessed the relationship between estimated glomerular filtration rate (eGFR) and tertiles of serum long-chain n-3 and n-6 PUFA profiles ([eicosapentaenoic acid {EPA} + docosahexaenoic acid {DHA}]:arachidonic acid [AA]). GFR was estimated by Japanese specific equations using serum creatinine and cystatin C (eGFR_cre and eGFR_cys). Using multivariate-adjusted linear regression models, we also assessed the relationships between eGFRs and several n-3 and n-6 PUFAs, which have been suggested to be associated with renal function.

Results

In all participants, higher dietary fish intake as assessed by a semi-quantitative questionnaire was associated with higher serum value of (EPA+DHA):AA. Participants in the higher (EPA+DHA):AA tertiles had non-significantly higher eGFR_cre and significantly higher eGFR_cys (P = 0.016). In addition, eGFR_cys in T₂+T₃ of (EPA+DHA):AA was significantly higher than that in T₁ (adjusted mean eGFR_cys, T₁: 87 ml/min/1.73 m², T₂+T₃: 91 ml/min/1.73 m²; P < 0.01). Among the PUFAs, only (EPA+DHA) was significantly associated with eGFR_cys.

Conclusions

Serum (EPA+DHA):AA, which reflects an individual’s fish intake, might be associated with eGFR_cys in Japanese community-dwellers.Key words: epidemiology, (EPA+DHA):AA, population-based study     

A high ratio of dietary n-3/n-6 polyunsaturated fatty acids improves obesity-linked inflammation and insulin resistance through suppressing activation of TLR4 in SD rats

Dietary ratios of n-3/n-6 polyunsaturated fatty acids (PUFAs) have been implicated in controlling markers of metabolic disorders, including obesity, insulin resistance (IR), inflammation, and lipid profiles, which are also presumed to be partly related to type 2 diabetes mellitus (T2DM). However, molecular mechanisms of the different PUFAs related to metabolic disorders have not been systematically addressed. The present study aimed to investigate the impact of dietary n-3/n-6 PUFA ratios on obesity and IR and, further, to determine the underlying mechanisms. For 16 weeks, 32 SD male rats, randomly divided into four groups (n = 8 per group), received one of the following diets: normal chow, high saturated fatty acid (SFA), high n-3/n-6 PUFA ratio (1∶1, PUFA^1:1), or low n-3/n-6 PUFA ratio (1∶4, PUFA^1:4). Following the experimental diet period, metabolic parameters related to obesity and IR were measured. Compared to SFA diet-fed rats, PUFA^1:1 diet-fed rats exhibited decreased body and visceral fat weight, lowered blood lipids, and improved glucose tolerance and insulin sensitivity. Interestingly, these changes were accompanied with decreased expression levels of circulating pro-inflammatory cytokines, including tumor necrosis factor α, interleukin-6, and C-reactive protein. Moreover, the TLR4 protein and mRNA levels were markedly down-regulated by PUFA^1:1 compared with SFA; however, PUFA^1:4 diet-fed rats failed to exhibit these changes. Cumulatively, our data highlight a role for a PUFA^1:1 diet in the prevention of obesity and related metabolic disorders by suppressing the activation of TLR4, a critical modulator of pro-inflammatory cytokines.     

肥胖小鼠DNA甲基化改变以及n-3多不饱和脂肪酸的影响作用

【目的】 探讨肥胖状态下脂肪组织基因组DNA甲基化及甲基转移酶表达改变以及n-3多不饱和脂肪酸(n-3 PUFAs)的影响作用。 【方法】 使用30只3~4周龄C57BL/6J雄性小鼠,随机分为3组,每组10只。小鼠分别给予两种高脂饲料(脂肪含量为34.9%,供能比为60%)-n-6 PUFAs(脂肪来源于葵花籽油)饲料和n-3 PUFAs(脂肪来源于鱼油)饲料喂养14周;以正常脂饲料(脂肪含量为4.3%,供能比为10%)(脂肪来源于葵花籽油)为对照。喂养结束后对小鼠脂肪组织基因组DNA总甲基化以及甲基转移酶(DNMTs)进行测定。 【结果】 与正常脂饲料喂养小鼠相比,两组高脂饲料诱导肥胖小鼠的脂肪组织DNA总甲基化程度均明显升高,但n-3 PUFAs高脂饲料组升高的程度显著低于n-6 PUFAs组。n-6 PUFAs高脂饲料诱导肥胖小鼠的脂肪组织DNMT1、DNMT3a和DNMT3b的表达均显著高于正常脂饲料组小鼠,而n-3 PUFAs高脂饲料喂养小鼠脂肪组织中这3种酶的表达无变化。 【结论】 肥胖状态下脂肪组织基因组DNA甲基化程度升高;鱼油n-3 PUFAs具有抑制DNA甲基化的作用。     

多不饱和脂肪酸对小鼠瘦素表达的影响

目的探讨多不饱和脂肪酸(PUFAs)对瘦素表达的影响。方法使用4w龄C57BL/6J雌性小鼠,分别给予不同种类高脂饲料(18%脂肪,供能比为36%)喂养-高脂豆油饲料、高脂鱼油饲料和高脂豆油:鱼油(5:1)混合饲料,以正常饲料(6%脂肪来自豆油,供能比为12%)为对照,小鼠自由进食,喂养时间为4个月。同时进行了PUFAs对体外培养3T3-L1细胞分化的干预实验,在细胞被诱导分化D5,在培养基中分别加入油酸(OA,C18:1n-9)、花生四烯酸(AA,C20:4n-6)、二十碳五烯酸(EPA,C20:5n-3)和二十二碳六烯酸(DHA,22:6n-3,0.125mmol/L)培养12h。采用酶联免疫吸附试验(ELISA)观察小鼠血浆和细胞培养基中瘦素及瘦素受体(sOB-R)表达的变化。结果鱼油组、豆油:鱼油组以及豆油组之间血浆瘦素水平(15.97±1.41,10.37±0.98和5.81±2.95μg/L)均存在显著性差异(鱼油>豆油:鱼油>豆油);与正常对照组(14.96±6.62μg/L)比,鱼油组血浆瘦素水平未发生明显变化。血浆sOB-R水平在4组饲料之间未见显著性差异。细胞培养显示,与对照组(18.70±0.67μg/gprot)比,在培养基中加入EPA和DHA后瘦素表达量(30.19±7.11和28.18±4.87μg/gprot)明显增多;而加入OA和AA对瘦素表达(19.75±6.11和24.48±9.84μg/gprot)无影响。值得注意的是,未能检测到细胞培养基中sOB-R的表达。结论饲料PUFAs对小鼠瘦素表达具有调节功能,但鱼油n-3PUFAs和豆油n-6PUFAs的作用不同。     

Dietary Lipids in Early Development and Intestinal Inflammatory Disease

Inflammatory bowel diseases are life-long reoccurring inflammatory disorders of the gastrointestinal tract and have been increasing in incidence in recent decades, notably in the pediatric population. Although genetic predisposition remains an important factor, this increased incidence most likely reflects an environmental change. One potential contributor to this is the change in dietary fat intake, with dietary intake of n-6 polyunsaturated fatty acids (PUFAs) following a similar temporal pattern to the change in inflammatory bowel disease incidence. Dietary n-6 PUFAs comprise a major, modifiable, environmental factor known to promote a heightened inflammatory response through a number of pathways, including their role as precursors for synthesis of eicosanoids and their inhibitory effect on the synthesis of the n-3 PUFAs eicosapentanoic acid and do-cosahexanoic acid. The increase in n-6PUFA intake affects individuals of all ages, with fetal PUFA accretion and infant dietary PUFA intake from breast milk reflecting maternal dietary intake. A high level of n-6 PUFA in milk results in increased n-6 PUFA in colonicphospholipids and an exaggerated inflammatory response to chemically induced colitis. Conversely, during development, a diet low in n-6 PUFAs and high in n-3 PUFAs increases colonic n-3 fatty acids, attenuates the inflammatory response, and lowers colonic damage. High dietary n-6 PUFA intake may be an important environmental modifier that contributes to inflammatory bowel diseases.