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.     

Erythrocyte membrane n-3 fatty acid levels and carotid atherosclerosis in Chinese men and women

Objective

Prospective studies have supported the beneficial effects of n-3 fatty acid consumption on cardiac deaths, but limited data focused on atherosclerosis. We investigated the associations between n-3 fatty acids in erythrocytes and atherosclerosis in middle-aged and older Chinese.

Methods

847 subjects (285 men and 562 women), aged 40–65 years, from Guangzhou, China were included in this community-based cross-sectional study between December 2005 and January 2008. The levels of α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in erythrocytes were measured by gas chromatography. Carotid ultrasound examination was conducted to obtain intima–media thickness of the common carotid artery and the carotid bifurcation. Dietary data and other covariates were collected using interviewer-administered questionnaires.

Results

After adjustment for age, sex, and other confounders, negative dose–response associations between the contents of individual n-3 polyunsaturated fatty acids in the erythrocyte membrane and the prevalence of carotid artery wall thickening and plaque were observed. A comparison in the highest and lowest tertiles gave odds ratios (95% confidence interval) for thickening in the walls of the common carotid artery of 0.58 (0. 34–0.97; P-trend = 0. 037) for DHA, and 0.39 (0.23–0.67; P-trend < 0.001) for ALA. However, EPA was not significantly associated with carotid atherosclerosis. Similar results were found for thickening at the carotid bifurcation and the occurrence of carotid artery plaque.

Conclusions

Higher levels of DHA and ALA in the erythrocyte membrane were significantly associated with a lower burden of subclinical atherosclerosis.     

Polyunsaturated fatty acids balance affects platelet NOX2 activity in patients with liver cirrhosis

BackgroundNADPH-oxidase-2 up-regulation has been suggested in liver damage perpetuation via an oxidative stress-mediated mechanism. n-6/n-3 polyunsaturated fatty acids ratio derangement has been reported in liver disease.AimTo explore polyunsaturated fatty acids balance and its interplay with platelet oxidative stress in liver cirrhosis.MethodsA cross-sectional study in 51 cirrhotic patients and sex- and age-matched controls was performed. Serum polyunsaturated fatty acids and oxidative stress markers (urinary isoprostanes and serum soluble NADPH-oxidase-2-derived peptide) were measured. The effect on platelet oxidative stress of n-6/n-3 polyunsaturated fatty acids ratio in vitro and in vivo (1-week supplementation with 3 g/daily n-3-polyunsaturated fatty acids) was tested.ResultsCompared to controls, cirrhotic patients had significantly higher n-6/n-3 polyunsaturated fatty acids ratio. n-6/n-3 polyunsaturated fatty acids ratio correlated significantly with disease severity and oxidative stress markers. In vitro experiments showed that in Child–Pugh C patients’ platelets incubation with low n-6/n-3 polyunsaturated fatty acids ratio resulted in dose-dependent decrease of radical oxigen species (−39%), isoprostanes (−25%) and NADPH-oxidase-2 regulation (−51%). n-3 polyunsaturated fatty acids supplemented patients showed significant oxidative stress indexes reduction.ConclusionsIn cirrhosis, n-6/n-3 polyunsaturated fatty acids imbalance up-regulates platelet NADPH-oxidase-2 with ensuing oxidative stress. Further study to evaluate if n-3 supplementation may reduce disease progression is warranted.     

铁死亡脂质过氧化机制及其与阿尔茨海默病的联系

<正>阿尔茨海默病（Alzheimer disease,AD）是多发于65岁及以上老年人群的中枢神经系统退行性疾病,临床表现以记忆、语言及其他认知能力衰退为主,主要病理特征为以β-淀粉样蛋白（amyloidβ-protein,Aβ）为核心成分的老年斑及tau蛋白过度磷酸化引起的神经原纤维缠结。在日益增强的老龄化趋势下,     

子痫前期产妇血液、胎盘和脐血中多不饱和脂肪酸含量与正常产妇的比较研究

目的:比较子痫前期产妇和正常产妇血液、胎盘和脐血中多不饱和脂肪酸(PUFA)含量的差别。方法:收集30例正常妊娠和30例子痫前期产妇血液、胎盘和脐血标本,采用石英毛细管柱气相色谱法测定两组产妇血液、胎盘和脐血中的多种脂肪酸成分并对其中5种PUFA[亚油酸(LA)、亚麻酸(ALA)、花生四烯酸(AA)、二十二碳五烯酸(EPA)、二十二碳六烯酸(DHA)]的绝对含量和百分含量进行比较。结果:子痫前期组产妇血中AA和DHA的绝对含量较正常妊娠组产妇高(P<0. 05),但其百分含量比较差异无统计学意义(P>0. 05)。产妇血中LA的百分含量在子痫前期组较正常妊娠组低(P<0. 05)。胎盘中AA/DHA的比值在子痫前期组较正常妊娠组产妇高(P<0. 05),胎盘中ALA的百分含量在子痫前期组较正常妊娠组高(P<0. 05);脐血中LA的百分含量在子痫前期组较正常妊娠组高(P<0. 05)。结论:子痫前期产妇血液、胎盘和脐血中PUFA的含量发生了改变,这些改变可能与子痫前期的发生有关,还有待进一步研究。     

Polyunsaturated fatty acids and gliomas: A critical review of experimental,clinical, and epidemiologic data

Certain polyunsaturated fatty acids (PUFAs) called essential fatty acids (EFAs) cannot be biosynthesized by the body and hence, need to be obtained from diet. These PUFAs and their metabolites have multiple physiological functions that are altered in tumor cells due to a decreased expression of Δdelta-6-desaturase, which is an essential step in their metabolism. As a result, tumor cells would be protected from the toxic effect caused by free radicals, one product of EFA metabolism. EFAs have been proposed to have therapeutic potential in the treatment of glioblastoma. Gliomas are the most common primary tumors of the central nervous system in children and adults. High-grade gliomas remain a therapeutic challenge in neuro-oncology because there is no treatment that achieves a significant improvement in survival. Novel therapeutic strategies that use PUFAs for the treatment of gliomas have been assessed in cell cultures, rodent glioma models, and humans, with encouraging results. Here we review the latest progress made in the field.     

Psychophysiological biomarkers explaining the association between depression and prognosis in coronary artery patients: A critical review of the literature

This paper aims to provide an overview of the current state of affairs on psychophysiological factors that may explain the link between depression and adverse outcome in coronary artery disease (CAD) patients. Factors discussed include heart rate variability, inflammation, platelet function, hypothalamus-pituitary-adrenal axis activity, serotonin metabolism and polyunsaturated fatty acids. Evidence suggests the involvement of each of these factors in both depression and CAD, together contributing to the prospective association between depression and cardiac outcome. Unfortunately, the involvement of above factors has been evaluated mostly in isolation, despite their functional interrelations and associations with behavioral factors. Moreover, there may be specific relations between individual symptoms of depression and certain psychophysiological mechanisms, rather than with general depression, further complicating the notion of depression as a cardiotoxic factor. The relatively understudied complexity of the relation between depression and CAD may serve as an explanation for the finding that depression treatment does not or barely affect cardiac outcome. Future studies should focus on the network of psychophysiological (and behavioral) factors to elucidate their precise role and timing in depressed cardiac patients.     

多不饱和脂肪酸对高碘所致胚胎损害的拮抗作用

目的：观察多不饱和脂肪酸对高碘所致胚胎损害的拮抗作用。方法：将小鼠随机分为适碘组,高碘组,高碘十多不饱和脂肪酸组（DHA,EPA）,分别饮含碘50,3000ug/L的去离子水,喂养3个月,令雌雄同笼,观察胚胎生长发育情况,结果：加多不饱和脂肪酸组甲状腺绝对重量和相对重量,畸胎率和颈椎异常均低于高碘组（P＜0．05）,而窝平均体重和窝平均胎盘重均高于高碘组（P＜0．005）,多不饱和脂肪酸组与适碘组相比,窝平均胎盘增加,结论：多不饱和脂肪酸对高碘所致胎胎损害有一定的秸抗作用。     

Prevention of alcoholic fatty liver and mitochondrial dysfunction in the rat by long-chain polyunsaturated fatty acids

BACKGROUND/AIMS: We reported that reduced dietary intake of polyunsaturated fatty acids (PUFA) such as arachidonic (AA,20:4n6,omega-6) and docosahexaenoic (DHA,22:6n3,omega-3) acids led to alcohol-induced fatty liver and fibrosis. This study was aimed at studying the mechanisms by which a DHA/AA-supplemented diet prevents alcohol-induced fatty liver. METHODS: Male Long-Evans rats were fed an ethanol or control liquid-diet with or without DHA/AA for 9 weeks. Plasma transaminase levels, liver histology, oxidative/nitrosative stress markers, and activities of oxidatively-modified mitochondrial proteins were evaluated. RESULTS: Chronic alcohol administration increased the degree of fatty liver but fatty liver decreased significantly in rats fed the alcohol-DHA/AA-supplemented diet. Alcohol exposure increased oxidative/nitrosative stress with elevated levels of ethanol-inducible CYP2E1, nitric oxide synthase, nitrite and mitochondrial hydrogen peroxide. However, these increments were normalized in rats fed the alcohol-DHA/AA-supplemented diet. The number of oxidatively-modified mitochondrial proteins was markedly increased following alcohol exposure but significantly reduced in rats fed the alcohol-DHA/AA-supplemented diet. The suppressed activities of mitochondrial aldehyde dehydrogenase, ATP synthase, and 3-ketoacyl-CoA thiolase in ethanol-exposed rats were also recovered in animals fed the ethanol-DHA/AA-supplemented diet. CONCLUSIONS: Addition of DHA/AA prevents alcohol-induced fatty liver and mitochondrial dysfunction in an animal model by protecting various mitochondrial enzymes most likely through reducing oxidative/nitrosative stress.