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肥胖小鼠雄性后代的代谢和黑素皮质素基因表达改变。

Metabolic and melanocortin gene expression alterations in male offspring of obese mice.

机构信息

Inserm, U855, Lyon, France.

出版信息

Mol Cell Endocrinol. 2010 May 5;319(1-2):99-108. doi: 10.1016/j.mce.2010.01.021. Epub 2010 Jan 25.

Abstract

To study the consequences of maternal obesity during gestation and suckling periods on metabolic features and expression of genes belonging to the melanocortinergic system, we developed Diet-Induced-Obesity (DIO) in mice fed high-fat-diet (HFD). After weaning, F1-descendants were fed the same diet than dams up to 16 weeks or received a 2-week standard chow at several time points. From birth, F1-DIO displayed higher body weight than F1-control. Hyperinsulinemia, hypertriglyceridemia, hyperleptinemia were detected from P10 and fasting hyperglycaemia from 2 week-post-weaning. From late gestation to 16-week-post-weaning the expression of MC4-R gene and/or the POMC/AgRP ratio was increased, suggesting an activation of this pathway to compensate the deleterious effects of HFD. Standard chow replacement at weaning normalized metabolic status but a partial recovery was obtained for later changes. Concomitant variations in the expression of the melanocortinergic genes were observed. Therefore, early nutritional intervention could override the impact of maternal and postnatal over-nutrition.

摘要

为了研究孕期和哺乳期母体肥胖对黑素皮质素能系统相关基因的表达和代谢特征的影响,我们用高脂肪饮食(HFD)诱导建立了肥胖模型(DIO)。断奶后,F1 后代接受与母鼠相同的饮食,直至 16 周,或在几个时间点接受为期 2 周的标准饮食。从出生起,F1-DIO 比 F1-control 的体重更高。从第 10 天开始,检测到高胰岛素血症、高三酰甘油血症和高瘦素血症,从断乳后 2 周开始出现空腹高血糖。从妊娠晚期到 16 周断奶后,MC4-R 基因的表达和/或 POMC/AgRP 比值增加,表明该途径的激活是为了补偿 HFD 的有害影响。断奶时用标准饮食替代可以使代谢状态正常化,但对于后期的变化只能部分恢复。同时观察到黑素皮质素能基因表达的变化。因此,早期的营养干预可以克服母体和产后过度营养的影响。

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