Maternal Betaine Supplementation during Gestation Enhances Expression of mtDNA-Encoded Genes through D-Loop DNA Hypomethylation in the Skeletal Muscle of Newborn Piglets

Abstract

Betaine has been widely used in animal and human nutrition to promote muscle growth and performance, yet it remains unknown whether maternal betaine supplementation during gestation affects the metabolic characteristics of neonatal skeletal muscles. In the present study, feeding sows with betaine-supplemented diets throughout gestation significantly upregulated the expression of mtDNA-encoded OXPHOS genes (p < 0.05), including COX1, COX2, and ND5, in the muscle of newborn piglets, which was associated with enhanced mitochondrial COX enzyme activity (p < 0.05). Concurrently, maternal betaine supplementation increased the plasma betaine concentration and muscle expression of methyl transfer enzymes (p < 0.05), BHMT and GNMT, in offspring piglets. Nevertheless, Dnmt3a was downregulated at the level of both mRNA and protein, which was associated with a hypomethylated mtDNA D-loop region (p < 0.05). These results suggest that maternal betaine supplementation during gestation enhances expression of mtDNA-encoded genes through D-loop DNA hypomethylation in the skeletal muscle of newborn piglets.

In ovo injection of betaine alleviates corticosterone-induced fatty liver in chickens through epigenetic modifications

“…The growth promoting effect of betaine observed in the present study was in agreement with the previous reports in neonatal piglets born to betaine-supplemented sows36. The mechanisms underlying the growth promoting effects of betaine involve stimulation of growth hormone (GH) secretion and autocrine/endocrine IGF-1 release2337.…”

Maternal betaine supplementation in rats induces intergenerational changes in hepatic IGF‐1 expression and DNA methylation

“…F1 showed a retarded growth and decreased body weight, which is in line with a previous finding that an excess methyl donor in the perinatal period significantly reduced the body weight of female rat offspring . However, other investigators reported conflicting results that methyl donor supplementation increased the fetal weight and birth weight in pigs, whereas maternal methyl donor restriction decreased the birth weight in rats . Interestingly, we found that maternal betaine supplementation in grand dams significantly increased the weaning weight of F2 offspring.…”

“…Additionally, we observed significantly increased F1 litter size and litter weight in betaine‐supplemented group. Again, this is against the previous reports that maternal methyl donor supplementation or restriction did not affect the litter size in pigs , but reduced litter size in rats . These inconsistent findings may be explained by differences in the types and levels of methyl donors, the time and period of supplementation, as well as the animal species and diet compositions.…”

Methyl donors dietary supplementation to gestating sows diet improves the growth rate of offspring and is associating with changes in expression and DNA methylation of insulin‐like growth factor‐1 gene

“…In line with previous observations in pigs (Oster et al., ; Jia et al., ; Simard et al., ) and rats (Konycheva et al., ), dietary MD supplementation to sows’ diet during pregnancy accelerated the growth of offspring, which was indicated by significantly higher BW at birth, weaning and finishing stage (180 days). In the present study, the composition of colostrum and milk (Supporting information Table S2), as well as feed intake and BW loss of sows (5.13 kg/day vs. 5.12 kg/day; 6.99 kg vs. 7.53 kg), were not changed by dietary treatment, indicating that there might be some internal changes, contributed to enhanced postnatal growth performance in the offspring pigs.…”