| 1. |
- Cai, Demin, et al.
(författare)
-
Epigenetic and SP1-mediated regulation is involved in the repression of galactokinase 1 gene in the liver of neonatal piglets born to betaine-supplemented sows
- 2017
-
Ingår i: European Journal of Nutrition. - : Springer Science and Business Media LLC. - 1436-6207 .- 1436-6215. ; 56:5, s. 1899-1909
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: In this study, we sought to investigate the effects of maternal betaine supplementation on the expression and regulation of GALK1 gene in the liver of neonatal piglets.Methods: Sixteen sows of two groups were fed control or betaine-supplemented diets (3 g/kg), respectively, throughout the pregnancy. Newborn piglets were individually weighed immediately after birth, and one male piglet close to mean body weight from the same litter was selected and killed before suckling. Serum samples of newborn piglets were analyzed for biochemical indexes, hormone and amino acid levels. Liver samples were analyzed for GALK1 expression by real-time PCR and western blotting, while GALK1 regulational mechanism was analyzed by methylated DNA immunoprecipitation, chromatin immunoprecipitation and microRNAs expression.Results: Betaine-exposed neonatal piglets had lower serum concentration of galactose, which was associated with significantly down-regulated hepatic GALK1 expression. The repression of GALK1 mRNA expression was associated with DNA hypermethylation and more enriched repression histone mark H3K27me3 on its promoter. Binding sites of SP1, GR and STAT3 were predicted on GALK1 promoter, and decreased SP1 protein content and lower SP1 binding to GALK1 promoter were detected in the liver of betaine-exposed piglets. Furthermore, the expression of miRNA-149 targeting GALK1 was up-regulated in the liver of betaine-exposed piglets, along with elevated miRNAs-processing enzymes Dicer and Ago2.Conclusions: Our results suggest that maternal dietary betaine supplementation during gestation suppresses GALK1 expression in the liver of neonatal piglets, which involves complex gene regulation mechanisms including DNA methylation, histone modification, miRNAs expression and SP1-mediated transcriptional modulation.
|
|
| 2. |
- Cai, Demin, et al.
(författare)
-
Nuclear Receptors in Hepatic Glucose and Lipid Metabolism During Neonatal and Adult Life
- 2017
-
Ingår i: Current protein and peptide science. - : BENTHAM SCIENCE PUBL LTD. - 1389-2037 .- 1875-5550. ; 18:6, s. 548-561
-
Forskningsöversikt (refereegranskat)abstract
- Research efforts focusing on metabolic diseases have established a close conjunction between glucolipid abnormalities and nuclear receptors, a large superfamily of receptors including classic peroxisome proliferation-activated receptors (PPARs), liver X receptors (LXRs), farnesoid X receptors (FXRs) and glucocorticoid receptors (GRs) together with burgeoning retinoic acid receptor-related orphan receptors (RORs) and REV-ERBs. Nuclear receptors are identified to control a series of physiological and pathological processes of glucose and lipid metabolism and also implicated to mediate the long-term effects of early environmental and nutritional experiences on the formation of adult chronic metabolic disorders in human and animals. Thus, nuclear receptors play profound roles in fetal programming and adult regulation of glucolipid metabolism. In this review, we provide an overview on the recent advances in the field of nuclear receptors focusing on their roles in lipid and glucose metabolism during early and late life courses. We hope that this knowledge may shed new lights on identifying the novel target molecules or pathways for the prevention and treatment of metabolic disorders involving disrupted glucose and lipid homeostasis in human and animals.
|
|
