Dataset Information

Epigenetics: intrauterine growth retardation (IUGR) modifies the histone code along the rat hepatic IGF-1 gene.

ABSTRACT: Intrauterine growth restriction (IUGR) decreases serum insulin growth factor-1 (IGF-1) levels. IGF-1 is an epigenetically regulated gene that has two promoters, alternative exon 5 splicing, and multiple termination sites. The regulation of gene expression involves the whole gene, as evidenced by the aforementioned IGF-1 paradigm. We hypothesized that IUGR in the rat would affect hepatic IGF-1 expression and alter the epigenetic characteristics of the IGF-1 gene along its length. IUGR was induced through a bilateral uterine artery ligation of the pregnant rat, a well-characterized model of IUGR. Pups from anesthesia and sham-operated dams were used as controls. Real-time RT-PCR and ELISA was used to measure expression at day of life (DOL) 0 and 21. Bisulfite sequencing and chromatin immunoprecipitation (ChIP) quantified IGF-1 epigenetic characteristics. A nontranscribed intergenic control was used for ChIP studies. IUGR decreased hepatic and serum IGF-1. Concurrently, IUGR modified epigenetic characteristics, particularly the histone code, along the length of the hepatic IGF-1 gene. Many changes persisted postnatally, and the postnatal effect of IUGR on the histone code was gender-specific. We conclude that IUGR modifies epigenetic characteristics of the rat hepatic IGF-1 gene along the length of the whole gene.

SUBMITTER: Fu Q

PROVIDER: S-EPMC2717764 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

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Epigenetics: intrauterine growth retardation (IUGR) modifies the histone code along the rat hepatic IGF-1 gene.

Fu Qi Q Yu Xing X Callaway Christopher W CW Lane Robert H RH McKnight Robert A RA

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20090413 8

Intrauterine growth restriction (IUGR) decreases serum insulin growth factor-1 (IGF-1) levels. IGF-1 is an epigenetically regulated gene that has two promoters, alternative exon 5 splicing, and multiple termination sites. The regulation of gene expression involves the whole gene, as evidenced by the aforementioned IGF-1 paradigm. We hypothesized that IUGR in the rat would affect hepatic IGF-1 expression and alter the epigenetic characteristics of the IGF-1 gene along its length. IUGR was induced ...[more]

PMID: 19364764

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Project description:Abnormal lipid metabolism, oxidative stress (OS), and inflammation play a pivotal role in the increased susceptibility to neonatal fatty liver diseases associated with intrauterine growth retardation (IUGR). This study was firstly conducted to investigate whether resveratrol could alleviate IUGR-induced hepatic lipid accumulation, alteration of redox and immune status in a sucking piglet model and explore the possible mechanisms at transcriptional levels. A total of 36 pairs of 7 d old male normal birth weight (NBW) and IUGR piglets were orally fed with either 80 mg resveratrol/kg body weight/d or 0.5% carboxymethylcellulose sodium for a period of 14 days, respectively. Compared with the NBW piglets, the IUGR piglets displayed compromised growth performance and liver weight, reduced plasma free fatty acid (FFA) level, increased hepatic OS, abnormal hepatic lipid accumulation and weakened hepatic immune function, and hepatic aberrant transcriptional expression of some genes such as heme oxygenase 1, superoxide dismutase 1, sterol regulatory element-binding protein 1c, stearoyl-CoA desaturase 1, liver fatty acid-binding proteins 1, toll-like receptor 4, and tumor necrosis factor alpha (TNF-α). Oral administration of resveratrol to piglets decreased the levels of FFA and total triglycerides (TG) in the plasma and hepatic TNF-α concentration, and increased glutathione reductase activity and reduced glutathione level in the liver. Resveratrol restored the increased alanine aminotransferase activity in the plasma of IUGR piglets. Treatment with resveratrol ameliorated the increased hepatic malondialdehyde, protein carbonyl, TG, and FFA concentrations induced by IUGR. Resveratrol treatment alleviated the reduced lipoprotein lipase activity and its mRNA expression as well as TNF-α gene expression in the liver of IUGR piglets. Hepatic glutathione peroxidase 1 and monocyte chemotactic protein 1 genes expression of piglets was upregulated by oral resveratrol administration. In conclusion, resveratrol administration plays a beneficial role in hepatic redox status and lipid balance of the IUGR piglets.

Dataset Information

Epigenetics: intrauterine growth retardation (IUGR) modifies the histone code along the rat hepatic IGF-1 gene.

Publications

Epigenetics: intrauterine growth retardation (IUGR) modifies the histone code along the rat hepatic IGF-1 gene.

Similar Datasets

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