Maternal Low-Protein Diet Affects Epigenetic Regulation of Hepatic Mitochondrial DNA Transcription in a Sex-Specific Manner in Newborn Piglets Associated with GR Binding to Its Promoter

Abstract

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.

Changes in milk performance and hepatic metabolism in mid-lactating dairy goats after being fed a high concentrate diet for 10 weeks

“…Significantly lower ruminal pH was observed in HC goats compared with LC goats, which was accompanied with greater VFA concentrations in ruminal fluids. These results were consistent with our previous studies (Dong et al, 2013;Jia et al, 2014;Tao et al, 2014;Tao et al, 2015). In those studies SARA were experimentally induced by feeding 65% concentrate diet for 2 months.…”

“…Cholesterol and TG were measured by commercial kits (E1015, E1013, respectively; Applygen Technologies Inc., Beijing, China) following the manufacturer's instructions. Concentrations of AMP, ADP, ATP, NAD and NADH in the liver were determined as described by Jia et al (2013). These parameters were analyzed by HPLC.…”

Lipopolysaccharide markedly changes glucose metabolism and mitochondrial function in the longissimus muscle of pigs

“…Measurement of ATP, ADP, AMP, NAD and NADH levels in longissimus dorsi muscle The measurement of AMP, ADP, ATP, NAD and NADH concentrations in muscle were performed as previously described (Jia et al, 2013). A total of 50 μg of frozen muscle sample were extracted using 1 ml lysate which containing 0.6 M perchloric acid and 1 mM EDTA.…”

α-Lipoic acid attenuates LPS-induced liver injury by improving mitochondrial function in association with GR mitochondrial DNA occupancy

“…It has been confirmed that GR is involved in the inflammatory response and plays an anti-inflammatory role [16,17]. GR was previously shown to translocate into the mitochondria and bind to the glucocorticoid response elements located in the mtDNA D-loop region [18,19], thereby exerting measurable effects on mitochondrial function [20]. However, the participation of GR in the LAmediated hepatic mitochondrial function effects during inflammation has never been investigated.…”