微藻异养产生二十碳五烯酸的新进展

二十碳五烯酸(Eicosapentaenoic acid简写EPA)是一种长链多不饱和脂肪酸，在营养强化、防治心血管疾病、减轻炎症等方面起着十分重要的作用。目前EPA主要来源于鱼油，很难满足市场对EPA日益增长的需求，必须寻求替代生产EPA的资源。一些微藻可在不需要光的条件下以廉价的有机物为原料异养生长，在异养条件下，可以很好地控制培养模式，有可能大规模地生产EPA。工业上用微藻生产EPA研究包括：筛选高EPA产量的微藻株，通过基因工程改善藻株，优化培养条件以及建立有效的培养体系。本文综述了近几年微藻在异养条件下生产EPA的最新进展，着重阐明硅藻是一种能在异养条件下生长且具有高EPA产率的模式藻株。     

Dietary fish oil,and to a lesser extent the fat-1 transgene,increases astrocyte activation in response to intracerebroventricular amyloid-β 1–40 in mice

Objectives: Increases in astrocytes and one of their markers, glial fibrillary acidic protein (GFAP) have been reported in the brains of patients with Alzheimer’s disease (AD). N-3 polyunsaturated fatty acids (PUFA) modulate neuroinflammation in animal models; however, their effect on astrocytes is unclear.

Methods: Fat-1 mice and their wildtype littermates were fed either a fish oil diet or a safflower oil diet deprived of n-3 PUFA. At 12 weeks, mice underwent intracerebroventricular infusion of amyloid-β 1-40. Astrocyte phenotype in the hippocampus was assessed at baseline and 10 days post-surgery using immunohistochemistry with various microscopy and image analysis techniques.

Results: GFAP increased in all groups in response to amyloid-β, with a greater increase in fish oil-fed mice than either fat-1 or wildtype safflower oil-fed mice. Astrocytes in this group were also more hypertrophic, suggesting increased activation. Both fat-1- and fish oil-fed mice had greater increases in branch number and length in response to amyloid-β infusion than wildtype safflower animals.

Conclusion: Fish oil feeding, and to a lesser extent the fat-1 transgene, enhances the astrocyte activation phenotype in response to amyloid-β 1-40. Astrocytes in mice fed fish oil were more activated in response to amyloid-β than in fat-1 mice despite similar levels of hippocampal n-3 PUFA, which suggests that other fatty acids or dietary factors contribute to this effect.     

High consumption of Ω-3 polyunsaturated fatty acids decrease plasma homocysteine: a meta-analysis of randomized, placebo-controlled trials

Objective

High consumption of ω-3 polyunsaturated fatty acids (PUFAs) has been associated with lower plasma homocystine (Hcy) levels, but intervention studies in humans have been inconclusive. The objective was to systematically evaluate the effects of ω-3 PUFA supplementation on plasma Hcy levels.

Methods

A comprehensive search of Medline, EMBASE, the Cochrane Clinical Trials Registry, and bibliographies of relevant articles published from 1966 through September 2010 was undertaken. All randomized, placebo-controlled trials that compared ω-3 PUFA supplementation with placebo were included. Two investigators performed data extraction and quality scoring independently, with discrepancies resolved by consensus.

Results

Eleven trials including 702 subjects were analyzed. The outcomes studied were plasma Hcy level. Eleven randomized, placebo-controlled trials were included in this meta-analysis. Supplementation with ω-3 PUFAs was associated with a significant decrease in plasma Hcy level (weighted mean difference −1.59 μmol/L, 95% confidence interval −2.34 to −0.83) compared with control subjects.

Conclusion

This meta-analysis suggested that ω-3 PUFA supplementation can decrease plasma Hcy levels. The implications of these findings remain to be elucidated.     

Altered lipid composition in cortical lipid rafts occurs at early stages of sporadic Alzheimer's disease and facilitates APP/BACE1 interactions

The presence of lipid alterations in lipid rafts from the frontal cortex in late stages of Alzheimer's disease (AD) has been recently demonstrated. Here, we have isolated and analyzed the lipid composition of lipid rafts from different brain areas from control and AD subjects at initial neuropathologic stages. We have observed that frontal cortex lipid rafts are profoundly altered in AD brains from the earliest stages of AD, namely AD I/II. These changes in the lipid matrix of lipid rafts affected both lipid classes and fatty acids and were also detected in the entorhinal cortex, but not in the cerebellum from the same subjects. Paralleling these changes, lipid rafts from AD frontal and entorhinal cortices displayed higher anisotropy for environment-sensitive probes, indicating that lipid changes in AD lipid rafts increased membrane order and viscosity in these domains. The pathophysiological consequences of these alterations in the development and progression of AD were strengthened by the significant, and specific, accumulation of β-secretase within the lipid rafts of AD subjects even at the earliest stages. Our results provide a mechanistic connection between lipid alterations in these microdomains and amyloidogenic processing of amyloid precursor protein.     

饮食中增加多不饱和脂肪酸对冠状动脉硬化性心脏病患者的影响

目的探讨饮食中增加多不饱和脂肪酸(PUFA)与冠状动脉硬化性心脏病(CHD)患病风险的关系。方法通过计算机检索PubMed、CENTRAL、中国生物医学文献数据库系统(CBM)、中国期刊全文数据库(CNKI)、万方数据库、中文科技期刊全文数据库(VIP)等,收集国内外公开发表的关于食物中增加PUFA与CHD患病风险关系的临床随机对照研究(RCT)。采用系统评价方法对各研究结果进行分析,计算其合并风险比(RR)和95%置信区间(CI)。结果检索到符合要求的文献7篇,包括13 257例受试者,在这些受试者中共有969例发生了CHD。在入选的研究中干预组受试者PUFA的平均摄入量为总热量的14.4%,对照组受试者PUFA的平均摄入量为总热量的5.0%。荟萃分析显示,饮食中增加PUFA可以明显减少CHD的患病风险(Z=13.15,P=0.000);干预组受试者CHD的患病风险可以减少19%(RR=0.81,95%CI:0.69～0.94,Z=13.5,P=0.000)。结论饮食中增加PUFA可以显著降低CHD患病风险。     

Dietary polyunsaturated fatty acids may increase plasma LDL-cholesterol and plasma cholesterol concentrations in carriers of an ABCG1 gene single nucleotide polymorphism: study in two Spanish populations

Background

ABCG1 mediates cellular cholesterol transport, but there is very little known about the influence of ABCG1 polymorphisms on human plasma lipoprotein cholesterol concentrations or on the interactions of these polymorphisms with diet.

Objective

Our objective was to investigate whether interactions between PUFA intake and ABCG1 polymorphisms modulate associations with plasma total cholesterol (TC), LDL- and HDL-cholesterol in two Spanish populations.

Methods

We grounded our investigation on two general population-based studies: the Hortega study (population A) and the Pizarra study (population B). Participants included 1178 individuals (50.0% women, age range 21–85 years) and 763 individuals (66% women, age range 23–73 years) from populations A and B, respectively, without lipid lowering drugs. Subjects were genotyped for ABCG1 variants. Biochemical measurements were taken by standard procedures. Dietary intakes were estimated with a validated questionnaire.

Results

In population A, the A allele homozygotes of SNP rs4148102 had higher TC and LDLc concentrations in subjects on a high PUFA diet than did the carriers of the G allele (242.1 ± 38.9 vs. 198.0 ± 36.0 mg/dL, p = 0.003, and 149.8 ± 37.9 vs. 111.4 ± 32.1 mg/dL, p = 0.005, respectively), and significant gene–diet interactions were observed (p = 0.020 and p = 0.013, respectively). In population B, similar differences in TC and LDLc concentrations were also found in association with this SNP under a high PUFA diet (253.2 ± 24.9 vs. 197.7 ± 39.9 mg/dL, p = 0.009, and 171.8 ± 20.5 vs. 120.4 ± 34.2 mg/dL, p = 0.004, respectively), but the gene–diet interactions observed were not significant (p = 0.379 and p = 0.422, respectively). In the pooled populations, differences in the TC and LDLc concentrations increased (246.8 ± 32.9 vs. 198.0 ± 37.5, p = 6 × 10⁻⁵, and 159.0 ± 32.6 vs. 114.3 ± 33.1, p = 3 × 10⁻⁵, respectively), and significant gene–diet interactions were maintained (p = 0.006 and p = 0.003, respectively).

Conclusion

In two Spanish populations, the ABCG1 polymorphism rs4148102 was associated with variations in plasma lipoprotein cholesterol concentrations in subjects with high PUFA intakes. Carriers of the AA genotype consuming high PUFA diet showed higher plasma LDLc concentrations.     

The effects of N-6 polyunsaturated fatty acid supplementation on the lipid composition and atherogenesis in mouse models of atherosclerosis

Despite numerous studies, the precise role of dietary n-6 polyunsaturated fatty acids in the pathogenesis of atherosclerosis remains controversial. It has been shown that feeding an n-6-enriched diet resulted in decreased atherosclerosis in African green monkeys and was associated with a reduction in LDL levels. However, other authors reported that n-6 supplementation increased the oxidative stress and the susceptibility of LDL to undergo in vitro oxidation, thus potentially enhancing atherosclerosis. The present study was designed to investigate the effect of dietary supplementation of n-6 polyunsaturated fats (safflower oil), as compared with a saturated fat-rich diet (Paigen), on the blood lipid profile and atherosclerosis in two mouse models. In the first experiment, female C57BL/6 mice (n=23–30 per group) were fed a cholate containing Paigen diet, a safflower oil-rich diet (with cholate), or normal chow for 15 weeks. No significant differences between the high fat diet groups were evident with respect to total cholesterol, LDL, HDL or triglyceride levels. The extent of aortic sinus fatty streaks did not differ significantly between the two groups. In the second experiment, LDL-receptor-deficient (LDL-RD) mice (n=20–30 per group) were randomized into similar dietary regimens. Mice consuming a safflower oil-enriched diet developed significantly less atherosclerosis, in comparison with Paigen diet-fed mice. A reduction in LDL levels, although not of a similar magnitude as the reduction in atherosclerosis, was evident in the safflower oil-fed mice when compared to the Paigen diet-fed littermates. In both mouse models of atherosclerosis, LDL isolated from the plasma of mice on the n-6 polyunsaturated diet was rendered slightly more susceptible to oxidation in vitro, as indicated by a shorter lag period for diene formation. Thus, the effects of n-6 fatty acids on the lipoprotein composition and other potential influences may have contributed to the anti-atherogenic effect in the LDL-RD mouse model.