Maternal Betaine Supplementation throughout Gestation and Lactation Modifies Hepatic Cholesterol Metabolic Genes in Weaning Piglets via AMPK/LXR-Mediated Pathway and Histone Modification

Cai, Demin; Yuan, Mengjie; Liu, Haoyu; Pan, Shifeng; Ma, Wenqiang; Jiang, Hong; Zhao, Ruqian

doi:10.3390/nu8100646

Cited by 24 publications

(13 citation statements)

References 50 publications

(56 reference statements)

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“…The postnatal stage, especially the weaning period, is of critical importance for animal growth and for health in adult life [47,48]. Based on our data and data from other studies, maternal nutrition programming modulates liver growth and function in offspring predominantly via epigenetic regulation [33,49,50]. Intriguingly, we demonstrated that the downregulated mRNA level of IGFBP-3 in the liver was associated with protein content.…”

Section: Discussionsupporting

confidence: 70%

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

Cong

Zhang

et al. 2019

Eur J Nutr

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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.

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Section: Discussionsupporting

confidence: 70%

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

Cong

Zhang

et al. 2019

Eur J Nutr

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“…Rats in the high-fat group showed a higher level of LDLR compared to the control group with betaine supplemented. Previous research reported that maternal dietary betaine supplementation upregulated the protein content of LDLR in rats and chickens and increased the gene expression of LDLR in piglets [26,47,48]. However, whether betaine could regulate serum LDLC levels increased by the high-fat diet via enhancing LDLR needs further research.…”

Section: Discussionmentioning

confidence: 95%

Dietary Betaine Addition Promotes Hepatic Cholesterol Synthesis, Bile Acid Conversion, and Export in Rats

Zhao

et al. 2020

Nutrients

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It is widely reported how betaine addition regulates lipid metabolism but how betaine affects cholesterol metabolism is still unknown. This study aimed to investigate the role of betaine in hepatic cholesterol metabolism of Sprague-Dawley rats. Rats were randomly allocated to four groups and fed with a basal diet or a high-fat diet with or without 1% betaine. The experiment lasted 28 days. The results showed that dietary betaine supplementation reduced the feed intake of rats with final weight unchanged. Serum low-density-lipoprotein cholesterol was increased with the high-fat diet. The high-fat diet promoted cholesterol synthesis and excretion by enhancing the HMG-CoA reductase and ABCG5/G8, respectively, which lead to a balance of hepatic cholesterol. Rats in betaine groups showed a higher level of hepatic total cholesterol. Dietary betaine addition enhanced cholesterol synthesis as well as conversion of bile acid from cholesterol by increasing the levels of HMGCR and CYP7A1. The high-fat diet decreased the level of bile salt export pump, while dietary betaine addition inhibited this decrease and promoted bile acid efflux and increased total bile acid levels in the intestine. In summary, dietary betaine addition promoted hepatic cholesterol metabolism, including cholesterol synthesis, conversion of bile acids, and bile acid export.

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“…SREBP-1a and SREBP-1c mainly facilitated fatty acid biosynthesis, while SREBP2 is considered to be essential for cholesterol uptake through LDL receptors and de novo cholesterol biosynthesis through mevalonate pathway (Song et al 2015). As sterol sensors, LXRs are responses to cellular sterol loading, forming obligate heterodimers with retinoid X receptors (RXRs) and triggering the expression of SREBP-1c and cholesterol efflux-related genes, and then induces triglyceride accumulation through fatty acid synthase (FAS) (Cai et al 2016). Meanwhile, cholesterol is one component of serum LDL, and is transported into liver through LDL receptor, and induces the expression of CYP7A1 and cholic acid biosynthesis (Saneyasu et al 2013).…”

Section: Discussionmentioning

confidence: 99%

Genetic Association of The CYP7A1 Gene with Duck Lipid Traits

Zhang

Qin

Luo

et al. 2018

Preprint

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Cholesterol 7α-hydroxylase (Cyp7a1) participates in lipid metabolism of liver, and its pathway involves catabolism of cholesterol to bile acids and excretion from the body. However, little is known about the effect of the polymorphisms of CYP7A1 gene on duck lipid traits. In the present study, seven novel synonymous mutations loci in exon 2 and exon 3 of CYP7A1 gene in Cherry Valley ducks were identified using PCR production direct sequencing. One novel SNP g.1033130 C>T was predicted in exon 2. Six novel SNPs g.1034076 C>T, g.1034334 G>A, g.1034373 G>A, g.1034448 T>C, g.1034541 C>G, and g.1034550 G>A were discovered in exon 3. Six haplotypes were detected using SHEsis online analysis software, and five loci (g.1034334G>A, g.1034373G>A, g.1034448T>C, g.1034541C>G, and g.1034550G>A) were in complete linkage disequilibrium, and as a block named Locus C3. By single SNP association analysis, we found that the g.1033130 C>T locus was significantly associated with IMF, AFP, TG, and TC (P<0.01 or P<0.05) respectively, the g.1034076 C>T locus was significantly associated with AFP (P<0.05), and the locus C3 was significantly associated with TCH (P<0.05). Sixteen dipoltypes were detected by the combination of haplotypes, and demonstrated strong association with IMF, AFP, TG, and TCH (P<0.01). Therefore, our data suggested that the seven SNPs of CYP7A1 gene are potential markers for lipid homeostasis, and may be used for early breeding and selection of duck.

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Maternal Betaine Supplementation throughout Gestation and Lactation Modifies Hepatic Cholesterol Metabolic Genes in Weaning Piglets via AMPK/LXR-Mediated Pathway and Histone Modification

Cited by 24 publications

References 50 publications

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

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

Dietary Betaine Addition Promotes Hepatic Cholesterol Synthesis, Bile Acid Conversion, and Export in Rats

Genetic Association of The CYP7A1 Gene with Duck Lipid Traits

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