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成年后代早期胆固醇暴露过度导致肝脏脂质代谢编程紊乱。

Malprogramming of Hepatic Lipid Metabolism due to Excessive Early Cholesterol Exposure in Adult Progeny.

机构信息

Department of Exercise and Nutrition Sciences, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY, 14214, USA.

Department of Biotechnical and Clinical Laboratory Sciences, University at Buffalo, Buffalo, NY, 14214, USA.

出版信息

Mol Nutr Food Res. 2019 Jan;63(2):e1800563. doi: 10.1002/mnfr.201800563. Epub 2018 Nov 26.

DOI:10.1002/mnfr.201800563
PMID:30447138
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6362455/
Abstract

SCOPE

The programming of hepatic lipid dysfunction in response to early cholesterol exposure and the influencing effects of postnatal diet is evaluated in apoE mice.

METHODS AND RESULTS

In two separate studies, female mice are assigned to a standard chow (S) or a cholesterol-enriched chow (C) diet during gestation and lactation. Male offspring from each dam are weaned on a postnatal S or a hypercaloric western (W) diet resulting in four experimental groups: S-S and C-S (Experiment 1) and S-W and C-W (Experiment 2). At weaning, litters from hypercholesterolemic mothers weighed less (p < 0.05) and pups had higher blood lipids, glucose, and hepatic cholesterol compared with pups from S-fed mothers. Adult C-S offspring demonstrate an atherogenic lipid profile and increased (p < 0.05) hepatic cholesterol and triglyceride content with altered lipid regulatory mRNA expression and protein content compared with S-S offspring. Alternatively, no difference (p > 0.05) is observed between S-W and C-W in serum and hepatic lipid profiles; however, serum AST and ALT are higher (p < 0.05) in C-W versus S-W offspring.

CONCLUSION

The degree of hepatic lipid deposition observed in adult offspring exposed to excessive early cholesterol is influenced by the postnatal diet.

摘要

范围

评估 apoE 小鼠对早期胆固醇暴露的肝脂功能障碍的编程以及产后饮食的影响。

方法和结果

在两项独立的研究中,雌性小鼠在妊娠期和哺乳期分别分配到标准饲料(S)或富含胆固醇的饲料(C)中。来自每个母体的雄性后代在产后 S 或高卡路里西式(W)饮食中断奶,导致四个实验组:S-S 和 C-S(实验 1)和 S-W 和 C-W(实验 2)。在断奶时,高胆固醇血症母亲的后代体重较轻(p<0.05),与来自 S 喂养母亲的后代相比,幼崽的血脂、血糖和肝胆固醇水平更高。与 S-S 后代相比,C-S 后代表现出致动脉粥样硬化的脂质谱,并增加(p<0.05)肝胆固醇和甘油三酯含量,以及改变的脂质调节 mRNA 表达和蛋白含量。相比之下,S-W 和 C-W 之间在血清和肝脂质谱中没有差异(p>0.05);然而,与 S-W 后代相比,C-W 后代的血清 AST 和 ALT 更高(p<0.05)。

结论

暴露于过量早期胆固醇的成年后代观察到的肝脂质沉积程度受产后饮食的影响。

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