Hepatic 1-carbon metabolism enzyme activity, intermediate metabolites, and growth in neonatal Holstein dairy calves are altered by maternal supply of methionine during late pregnancy

ملخص البحث

Hepatic 1-carbon metabolism enzyme activity, intermediate metabolites, and growth in neonatal Holstein dairy calves are altered by maternal supply of methionine during late pregnancy Abstract: Maternal supply of methyl donors such as methionine (Met) during late-pregnancy can affect offspring growth and development. The objective was to investigate the impact of post-ruminal Met supply during late-pregnancy on 1-carbon, Met cycle, and transsulfuration pathways in calf liver. During the last 28 d of pregnancy, cows were individually fed a control diet (CON) or the control diet plus rumen-protected D, L-Met (MET; 0.09% dry matter intake). Liver samples obtained from calves (n = 14/group) at 4, 14, 28, and 50 d of age were used for metabolomics, RT-PCR, and enzyme activity analyses. Genes associated with one-carbon metabolism, DNA methylation, and the CDPcholine pathway were analyzed via RT-PCR. Activity of betaine homocysteine methyltransferase (BHMT), cystathionine β-synthase (CBS), and 5-methyltetrahydrofolate homocysteine methyltransferase (MTR) was analyzed using 14 C isotopes. Data were analyzed using a mixed model that included the fixed effects of maternal treatment, day, and their interaction and the random effect was calf within (maternal diet). Calves born to dams offered MET tended to have greater birth body weight and had overall greater body weight during the first 9 wk of life. However, no differences were detected for daily feed intake and average daily gain between groups. Concentrations of betaine and choline, reflecting Met cycle activity, at d 14 through 28 were greater in MET calves. Transsulfuration pathway intermediates also were altered in MET calves, with concentrations of cysteinesulfinic acid and hypotaurine (d 4 and 14) and taurine being greater (4, 14, 28, and 50 d). Despite the lack of differences in daily feed intake, the greater concentrations of the TCA cycle intermediates fumarate and glutamate along with NAD/NADH in MET calves indicated enhanced rates of energy metabolism. Although activity of BHMT was greater in MET calves at d 14, CBS was lower, and increased at d 14 and 28 where it was greater compared with CON. Activity of MTR was lower at d 4 and 50 in MET calves. Among gene targets measured, MET calves had greater overall expression of MTR, phosphatidylethanolamine N-methyltransferase, and choline kinase α and β. An interaction of maternal diet x time was detected for mRNA abundance of DNA methyltransferase 3 alpha (involved in de novo methylation) due to namely to greater values at 4 and 14 in MET calves. Overall, data indicate that enhanced post-ruminal supply of Met to cows during late-pregnancy may program hepatic metabolism of the calf in the context of maintaining Met homeostasis, phosphatidylcholine and taurine synthesis, DNA methylation, and energy metabolism. These alterations potentially result in better efficiency of nutrient use, hence, conferring the calf a physiologic advantage during a period of rapid growth and development. The precise biologic mechanisms remain to be established.

الكلمات المفتاحيه

epigenetics, metabolism, methyl donor