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Maternal high-protein diet modulates hepatic growth axis in weaning piglets by reprogramming the IGFBP-3 gene.

ABSTRACT: PURPOSE:The aim of this study was to investigate the effects of maternal high dietary protein intake on the hepatic growth axis in offspring. METHODS:Fourteen primiparous purebred Meishan sows were fed either a standard-protein (SP, n?=?7) diet or a high-protein (HP, 150% of SP, n?=?7) diet during pregnancy. Offspring (one male and one female per group, n?=?14) on day 70 of the embryonic stage and on days 1, 35 and 180 after birth were selected, weighed and killed. Serum samples were analyzed for Tch, insulin and insulin-like growth factor-binding protein 3 (IGFBP-3) levels. Liver samples were analyzed for IGFBP-3 and IGF-I mRNA expression by qRT-PCR and for IGFBP-3, IGF1R and growth hormone receptor (GHR) protein expression by Western blotting. The underlying mechanism of IGFBP-3 regulation was determined by methylated DNA immunoprecipitation (MeDIP) and chromatin immunoprecipitation (ChIP). RESULTS:High-protein exposure resulted in significantly higher body and liver weights of piglets, and it increased their serum T3 and T4 levels at birth and/or at weaning. Furthermore, the IGFBP-3 protein content in the liver and serum was significantly reduced in the HP-exposed weaning piglets, whereas at the transcriptional level IGFBP-3 mRNA expression was downregulated in the livers of HP group piglets. Finally, DNA hypermethylation and higher enrichment of the histone repressive marks H3K27me3 and H3K9me3 were observed. CONCLUSIONS:Taken together, these results suggest that a maternal high-protein diet during gestation epigenetically reprograms IGFBP-3 gene expression to modulate the hepatic growth axis in weaning piglets.

SUBMITTER: Cong R

PROVIDER: S-EPMC7413878 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Maternal high-protein diet modulates hepatic growth axis in weaning piglets by reprogramming the IGFBP-3 gene.

Cong Rihua R Qu Xiaoli X Zhang Hui H Hu Yongling Y Ye Silin S Cai Demin D Li Xian X Liu Hao-Yu HY

European journal of nutrition 20190930 6

<h4>Purpose</h4>The aim of this study was to investigate the effects of maternal high dietary protein intake on the hepatic growth axis in offspring.<h4>Methods</h4>Fourteen primiparous purebred Meishan sows were fed either a standard-protein (SP, n = 7) diet or a high-protein (HP, 150% of SP, n = 7) diet during pregnancy. Offspring (one male and one female per group, n = 14) on day 70 of the embryonic stage and on days 1, 35 and 180 after birth were selected, weighed and killed. Serum samples w ...[more]

PMID: 31570976

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Project description:AimsObesity during pregnancy increases risk of cardiovascular disease (CVD) in the offspring and individuals exposed to over-nutrition during fetal life are likely to be exposed to a calorie-rich environment postnatally. Here, we established the consequences of combined exposure to a maternal and post-weaning obesogenic diet on offspring cardiac structure and function using an established mouse model of maternal diet-induced obesity.Methods and resultsThe impact of the maternal and postnatal environment on the offspring metabolic profile, arterial blood pressure, cardiac structure, and function was assessed in 8-week-old C57BL/6 male mice. Measurement of cardiomyocyte cell area, the transcriptional re-activation of cardiac fetal genes as well as genes involved in the regulation of contractile function and matrix remodelling in the adult heart were determined as potential mediators of effects on cardiac function. In the adult offspring: a post-weaning obesogenic diet coupled with exposure to maternal obesity increased serum insulin (P < 0.0001) and leptin levels (P < 0.0001); maternal obesity (P = 0.001) and a post-weaning obesogenic diet (P = 0.002) increased absolute heart weight; maternal obesity (P = 0.01) and offspring obesity (P = 0.01) caused cardiac dysfunction but effects were not additive; cardiac dysfunction resulting from maternal obesity was associated with re-expression of cardiac fetal genes (Myh7: Myh6 ratio; P = 0.0004), however, these genes were not affected by offspring diet; maternal obesity (P = 0.02); and offspring obesity (P = 0.05) caused hypertension and effects were additive.ConclusionsMaternal diet-induced obesity and offspring obesity independently promote cardiac dysfunction and hypertension in adult male progeny. Exposure to maternal obesity alone programmed cardiac dysfunction, associated with hallmarks of pathological left ventricular hypertrophy, including increased cardiomyocyte area, upregulation of fetal genes, and remodelling of cardiac structure. These data highlight that the perinatal period is just as important as adult-onset obesity in predicting CVD risk. Therefore, early developmental periods are key intervention windows to reduce the prevalence of CVD.

Dataset Information

Maternal high-protein diet modulates hepatic growth axis in weaning piglets by reprogramming the IGFBP-3 gene.

Publications

Maternal high-protein diet modulates hepatic growth axis in weaning piglets by reprogramming the IGFBP-3 gene.

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