title: Glucose metabolism and hepatic Igf1 DNA methylation are altered in the offspring of dams fed a low-salt diet during pregnancy.
abstract: 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.
authors.affiliation: Department of Internal Medicine, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Flavia R
authors.initials: FR
authors.lastname: Siqueira
authors.affiliation: Department of Internal Medicine, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Luzia N S
authors.initials: LN
authors.lastname: Furukawa
authors.affiliation: Department of Internal Medicine, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Ivone B
authors.initials: IB
authors.lastname: Oliveira
authors.affiliation: Department of Internal Medicine, University of São Paulo School of Medicine, São Paulo, Brazil. Electronic address: jheimann@usp.br.
authors.forename: Joel C
authors.initials: JC
authors.lastname: Heimann
mesh_terms: D000818:Animals; D005260:Female; D008297:Male; D011247:Pregnancy; D051381:Rats; D000367:Age Factors; D000831:Animals, Newborn; D001786:Blood Glucose / Q000187:drug effects; D004039:Diet, Sodium-Restricted; D019175:DNA Methylation / Q000187:drug effects / Q000502:physiology; D005215:Fasting / Q000097:blood; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005951:Glucose Tolerance Test; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology; D017208:Rats, Wistar; D017673:Sodium Chloride, Dietary / Q000494:pharmacology; D018709:Statistics, Nonparametric
chemical_list: D001786:Blood Glucose; D007334:Insulin-Like Growth Factor I; D017673:Sodium Chloride, Dietary
keywords: DNA methylation; Epigenetics; Fetal programming; Glucose metabolism; Insulin-like growth factor 1; Low-salt diet