Glucose-6-phosphatase (G6PC) plays an important role in glucose homeostasis because it catalyzes the final steps of gluconeogenesis and glycogenolysis. Maternal malnutrition during pregnancy affects G6PC activity, yet it is unknown whether epigenetic regulations of the G6PC gene are also affected. In this study, we fed primiparous, purebred Meishan sows either standard-protein (SP; 12% crude protein) or low-protein (LP; 6% crude protein) diets throughout gestation and analyzed hepatic G6PC expression in both male and female newborn piglets. The epigenetic regulation of G6PC, including DNA methylation, histone modifications, and micro RNA (miRNA), was determined to reveal potential mechanisms. Male, but not female, LP piglets had a significantly lower serum glucose concentration and greater hepatic G6PC mRNA expression and enzyme activity. Also, in LP males, glucocorticoid receptor binding to the G6PC promoter was lower compared with SP males, which was accompanied by hypomethylation of the G6PC promoter. Modifications in histones also were gender dependent; LP males had less histone H3 and histone H3 lysine 9 trimethylation and more histone H3 acetylation and histone H3 lysine 4 trimethylation on the G6PC promoter compared with the SP males, whereas LP females had more H3 and greater H3 methylation compared with their SP counterparts. Moreover, two miRNA, ssc-miR-339-5p and ssc-miR-532-3p, targeting the G6PC 3' untranslated region were significantly upregulated by the LP diet only in females. These results suggest that a maternal LP diet during pregnancy causes hepatic activation of G6PC gene expression in male piglets, which possibly contributes to adult-onset hyperglycemia.

K n m i U e , TN37996This paper reviews recent studies on the mechanism of corona treatment of polyolefin fi.lms, specifically the chemical and physical changes of this process and the self-adhesion mechanism. Corona discharge of polymeric films introduces polar groups into the surfaces, which increases the surface energy and, as a consequence, improves substrate wettability and adhesion. The main chemical mechanism of corona treatment is oxidation. In addition, corona treatment can crosslink surface regions and increase the film cohesive strength.

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Peroxisome proliferator-activated receptor α (PPARα) plays a protective role against non-alcoholic fatty liver disease (NAFLD). Sodium butyrate (NaB) has been shown to alleviate NAFLD, yet whether and how PPARα is involved in the action of NaB remains elusive. In this study, NaB administration alleviated high-fat-diet-induced NAFLD in adult rats, with a decrease of hepatic triglyceride content from 108.18 ± 5.77 to 81.34 ± 7.94 μg/mg ( p < 0.05), which was associated with a significant activation of PPARα. Nuclear factor κ-light-chain-enhancer of activated B cell (NF-κB)-mediated nucleotide-binding domain-like receptor protein 3 signaling and pro-inflammatory cytokine release were diminished by NaB treatment. NaB-induced PPARα upregulation coincided with a reduced protein content of histone deacetylase 1 and promoted histone H3 acetyl K9 (H3K9Ac) modification on the promoter of PPARα, whereas NaB-induced suppression of inflammation was linked to significantly increased PPARα binding with p-p65. NaB acts as a histone deacetylase inhibitor to upregulate PPARα expression with enhanced H3K9Ac modification on it promoter. NaB-induced PPARα activation stimulates fatty acid β oxidation and inhibits NF-κB-mediated inflammation pathways via protein-protein interaction, thus contributing to amelioration of high-fat-diet-induced NAFLD in adult rats.

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Betaine is reported to regulate hepatic cholesterol metabolism in mammals. Chicken eggs contain considerable amount of betaine, yet it remains unknown whether and how betaine in the egg affects hepatic cholesterol metabolism in chicks. In this study, eggs were injected with betaine at 2.5 mg/egg and the hepatic cholesterol metabolism was investigated in newly hatched chicks. Betaine did not affect body weight or liver weight, but significantly increased the serum concentration (P < 0.05) and the hepatic content (P < 0.01) of cholesterol. Accordingly, the cholesterol biosynthetic enzyme HMGCR was up-regulated (P < 0.05 for both mRNA and protein), while CYP7A1 which converts cholesterol to bile acids was down-regulated (P < 0.05 for mRNA and P = 0.07 for protein). Moreover, hepatic protein content of the sterol-regulatory element binding protein 1 which regulates cholesterol and lipid biosynthesis, and the mRNA abundance of ATP binding cassette sub-family A member 1 (ABCA1) which mediates cholesterol counter transport were significantly (P < 0.05) increased in betaine-treated chicks. Meanwhile, hepatic protein contents of DNA methyltransferases 1 and adenosylhomocysteinase-like 1 were increased (P < 0.05), which was associated with global genomic DNA hypermethylation (P < 0.05) and diminished gene repression mark histone H3 lysine 27 trimethylation (P < 0.05). Furthermore, CpG methylation level on gene promoters was found to be increased (P < 0.05) for CYP7A1 yet decreased (P < 0.05) for ABCA1. These results indicate that in ovo betaine injection regulates hepatic cholesterol metabolism in chicks through epigenetic mechanisms including DNA and histone methylations.

Mitochondrial oxidative phosphorylation (OXPHOS) plays an important role in energy homeostasis by controlling electron transfer and ATP generation. Maternal malnutrition during pregnancy affects mitochondrial (mt) DNA-encoded OXPHOS activity in offspring, yet it is unknown whether epigenetic mechanism is involved in the transcriptional regulation of mtDNA-encoded OXPHOS genes. In this study, 14 primiparous purebred Meishan sows were fed either standard- (SP, 12% crude protein) or low-protein (LP; 6% crude protein) diets throughout gestation, and the hepatic expression and transcriptional regulation of mtDNA-encoded OXPHOS genes were analyzed in newborn piglets. Maternal low protein diet decreased hepatic mtDNA copy number in males, but not in females. LP male piglets had significantly higher hepatic AMP concentration and low energy charge, which was accompanied by enhanced mRNA expression of NADH dehydrogenase subunits 6, cytochrome c oxidase subunit 1, 2, 3 and cytochrome b, as well as increased cytochrome c oxidase enzyme activity. In contrast, LP female piglets showed significantly lower hepatic AMP concentrations and higher energy charge with no alterations in OXPHOS gene expression. Moreover, LP males demonstrated higher glucocorticoid receptor (GR) binding to the mtDNA promoter compared with SP males, which was accompanied by lower cytosine methylation and hydroxymethylation on mtDNA promoter. Interestingly, opposite changes were seen in females, which showed diminished GR binding and enriched cytosine methylation and hydroxymethylation on mtDNA promoter. These results suggest that maternal low protein diet during pregnancy causes sex-dependent epigenetic alterations in mtDNA-encoded OXPHOS gene expression, possibly GR is involved in mtDNA transcription regulation.