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孕期和哺乳期母体高胆固醇血症及植物甾醇干预对叙利亚金仓鼠后代血脂异常和肝脏脂质代谢的影响

Influence of maternal hypercholesterolemia and phytosterol intervention during gestation and lactation on dyslipidemia and hepatic lipid metabolism in offspring of Syrian golden hamsters.

作者信息

Liu Jie, Iqbal Aadil, Raslawsky Amy, Browne Richard W, Patel Mulchand S, Rideout Todd C

机构信息

Department of Exercise and Nutrition Sciences, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY, USA.

Department of Biotechnical and Clinical Laboratory Sciences, University at Buffalo, Buffalo, NY, USA.

出版信息

Mol Nutr Food Res. 2016 Oct;60(10):2151-2160. doi: 10.1002/mnfr.201600116. Epub 2016 Jun 23.

DOI:10.1002/mnfr.201600116
PMID:27213832
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5056807/
Abstract

SCOPE

Although there is a normal physiological rise in maternal lipids during pregnancy, excessive maternal hyperlipidemia during pregnancy increases cardiovascular disease risk for both the mother and offspring. There are limited safe lipid-lowering treatment options for use during pregnancy, therefore, we evaluated the influence of maternal phytosterol (PS) supplementation on lipid and lipoprotein metabolism in mothers and progeny.

METHODS AND RESULTS

Female Syrian golden hamsters were randomly assigned to three diets throughout prepregnancy, gestation, and lactation (n = 6/group): (i) Chow (Chow), (ii) chow with 0.5% cholesterol (CH), and (iii) chow with 0.5% CH and 2% PS (CH/PS). Compared with newly weaned pups from Chow dams, pups from dams fed the CH-enriched diet demonstrated increases (p < 0.05) in total-C, LDL-C, HDL-C, and total LDL and VLDL particle number. Pups from CH-fed mothers also exhibited higher hepatic CH concentration and differential mRNA expression pattern of CH regulatory genes. Pups from PS-supplemented dams demonstrated reductions (p < 0.05) in serum total-C, non-HDL-C, and LDL-C but also increased triglycerides compared with pups from CH-fed dams. Maternal PS supplementation reduced (p < 0.05) hepatic CH and increased the abundance of HMG-CoAr and LDLr protein in newly weaned pups compared with the CH group.

CONCLUSION

Results suggest that maternal PS supplementation is largely effective in normalizing CH in pups born to mothers with hypercholesterolemia, however, the cause and long-term influence of increased triglyceride is not known.

摘要

范围

尽管孕期母体血脂会出现正常的生理性升高,但孕期母体高脂血症会增加母亲和后代患心血管疾病的风险。孕期安全的降脂治疗选择有限,因此,我们评估了母体补充植物甾醇(PS)对母亲及其后代脂质和脂蛋白代谢的影响。

方法与结果

雌性叙利亚金仓鼠在孕前、孕期和哺乳期被随机分为三种饮食组(每组n = 6):(i)普通饲料(Chow),(ii)含0.5%胆固醇的普通饲料(CH),以及(iii)含0.5% CH和2% PS的普通饲料(CH/PS)。与Chow组母鼠新断奶的幼崽相比,喂食富含CH饮食的母鼠所生幼崽的总胆固醇(total-C)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)以及总LDL和极低密度脂蛋白(VLDL)颗粒数均增加(p < 0.05)。CH喂养的母鼠所生幼崽的肝脏CH浓度也较高,且CH调节基因的mRNA表达模式存在差异。与CH喂养的母鼠所生幼崽相比,补充PS的母鼠所生幼崽的血清总胆固醇、非HDL-C和LDL-C降低(p < 0.05),但甘油三酯增加。与CH组相比,母体补充PS可降低新断奶幼崽肝脏中的CH含量,并增加3-羟基-3-甲基戊二酰辅酶A还原酶(HMG-CoAr)和低密度脂蛋白受体(LDLr)蛋白的丰度。

结论

结果表明,母体补充PS在很大程度上可使高胆固醇血症母亲所生幼崽的CH恢复正常,然而,甘油三酯升高的原因及其长期影响尚不清楚。

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Serum TG-lowering properties of plant sterols and stanols are associated with decreased hepatic VLDL secretion.植物甾醇和甾烷醇降低血清甘油三酯的特性与肝脏极低密度脂蛋白分泌减少有关。
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Alpha-lipoic acid reduces LDL-particle number and PCSK9 concentrations in high-fat fed obese Zucker rats.α-硫辛酸可降低高脂喂养的肥胖Zucker大鼠的低密度脂蛋白颗粒数量和前蛋白转化酶枯草溶菌素9(PCSK9)浓度。
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