Siqueira Flavia R, Furukawa Luzia N S, Oliveira Ivone B, Heimann Joel C
Department of Internal Medicine, University of São Paulo School of Medicine, São Paulo, Brazil.
Department of Internal Medicine, University of São Paulo School of Medicine, São Paulo, Brazil.
Physiol Behav. 2016 Feb 1;154:68-75. doi: 10.1016/j.physbeh.2015.11.013. Epub 2015 Nov 17.
A low-salt (LS) diet during pregnancy has been linked to insulin resistance in adult offspring, at least in the experimental setting. However, it remains unclear if this effect is due to salt restriction during early or late pregnancy. To better understand this phenomenon, 12-week-old female Wistar rats were fed a LS or normal-salt (NS) diet during gestation or a LS diet during either the first (LS10) or second (LS20) half of gestation. Glucose tolerance test, HOMA-IR, gene expression analysis and DNA methylation measurements were conducted for the Insr, Igf1, Igf1r, Ins1 and Ins2 genes in the livers of neonates and in the liver, white adipose tissue and muscle of 20-week-old male offspring. Birth weight was lower in the LS20 and LS animals compared with the NS and LS10 rats. In the liver, the Igf1 levels in the LS10, LS20 and LS neonates were lower than those in the NS neonates. Methylation of the Insr, Igf1r, Ins1 and Ins2 genes was influenced in a variable manner by low salt intake during pregnancy. Increased liver Igf1 methylation was observed in the LS and LS20 neonates compared with their NS and LS10 counterparts. Glucose intolerance was observed in adult offspring as an effect of low salt intake over the duration of pregnancy. Compared to the NS animals, the HOMA-IR was higher in the 12-week-old LS and 20-week-old LS-10 rats. Based on these results, it appears that the reason a LS diet during pregnancy induces a low birth weight is its negative correlation with Igf1 DNA methylation in neonates.
至少在实验环境中，孕期低盐（LS）饮食与成年后代的胰岛素抵抗有关。然而，这种影响是由于妊娠早期还是晚期的盐限制尚不清楚。为了更好地理解这一现象，对12周龄的雌性Wistar大鼠在妊娠期给予LS或正常盐（NS）饮食，或在妊娠的前半段（LS10）或后半段（LS20）给予LS饮食。对新生儿肝脏以及20周龄雄性后代的肝脏、白色脂肪组织和肌肉中的Insr、Igf1、Igf1r、Ins1和Ins2基因进行了葡萄糖耐量试验、HOMA-IR、基因表达分析和DNA甲基化测量。与NS和LS10大鼠相比，LS20和LS组动物的出生体重较低。在肝脏中，LS10、LS20和LS组新生儿的Igf1水平低于NS组新生儿。孕期低盐摄入对Insr、Igf1r、Ins1和Ins2基因的甲基化有不同程度的影响。与NS和LS10组相比，LS和LS20组新生儿肝脏中Igf1甲基化增加。成年后代出现葡萄糖不耐受是孕期低盐摄入的结果。与NS组动物相比，12周龄的LS组和20周龄的LS-10组大鼠的HOMA-IR更高。基于这些结果，孕期LS饮食导致低出生体重的原因似乎是其与新生儿Igf1 DNA甲基化呈负相关。
