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 effect of postruminal Met supply during late pregnancy on 1-carbon, Met cycle, and transsulfuration pathways in the calf liver. During the last 28 d of pregnancy, cows were individually fed a control diet or the control diet plus rumen-protected dl-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, real-time PCR, and enzyme activity analyses. Genes associated with 1-carbon metabolism, DNA methylation, and the cytidine 5′-diphosphocholine-choline pathway were analyzed via real-time PCR. Activity of betaine homocysteine methyltransferase, cystathionine β-synthase, 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 cysteine sulfinic acid and hypotaurine (d 4 and 14) and taurine being greater (d 4, 14, 28, and 50). Despite the lack of differences in daily feed intake, the greater concentrations of the tricarboxylic acid cycle intermediates fumarate and glutamate along with NAD/NADH in MET calves indicated enhanced rates of energy metabolism. Although activity of betaine homocysteine methyltransferase was greater in MET calves at d 14, cystathionine β-synthase was lower and increased at d 14 and 28, where it was greater compared with the control diet. 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 by time was detected for mRNA abundance of DNA methyltransferase 3α (involved in de novo methylation) due to greater values at d 4 and 14 in MET calves. Overall, the data indicate that enhanced postruminal 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.

Multifaceted role of one-carbon metabolism on immunometabolic control and growth during pregnancy, lactation and the neonatal period in dairy cattle

“…Xue and Snoswell [77] observed that hepatic BHMT activity in lambs increased with age until a ruminant state was reached, whereas MTR activity had a pattern that was opposite to BHMT. In dairy calves, a similar response was observed with BHMT activity increasing between 4 and 14 d of age and decreasing between 28 and 50 d of age [78,79]. The changes in activity over time in pre-ruminants are likely linked to the establishment of a functional ruminal microbiome, which leads to increased vitamin B 12 biosynthesis, a cofactor of MTR.…”

Amino acids and the regulation of oxidative stress and immune function in dairy cattle

“…Throughout the preweaning period, calves born to dams supplemented with RPM during late gestation had greater in vitro neutrophil phagocytosis, suggesting a priming effect of maternal Met supplementation on calf immune function ( Alharthi et al, 2019b ). Maternal Met supply also increased the hepatic activity of CBS and the concentrations of taurine compared with control calves, suggesting a greater flux of the transsulfuration pathways and a better antioxidant response with maternal Met supply ( Alharthi et al, 2019a ). Additionally, in another study, maternal Met supply during late gestation led to lower expression of TNF-α and MPO in PMNL at birth, while TLR2 , NOS 2, and cell adhesion molecule 1 were lower throughout the preweaning period ( Jacometo et al, 2018 ).…”

Maternal supplementation with cobalt sources, folic acid, and rumen-protected methionine and its effects on molecular and functional correlates of the immune system in neonatal Holstein calves

“…For instance, several studies with dietary methyl donors (e.g., methionine, choline, and folic acid) in peripartal dairy cows have confirmed benefits in performance, health, and immune function (Graulet et al, 2007;Osorio et al, 2013a;Vailati-Riboni et al, 2017b;Arshad et al, 2020). Many of these benefits were also linked to positive responses on aspects of energy metabolism, inflammation, antioxidant status, and birth BW in the offspring (Jacometo et al, 2016;Alharthi et al, 2019a;Duplessis and Girard, 2019), underscoring that adequate supply of methyl donors during later stages of fetal life is an important determinant of immunocompetence and growth in the neonatal calf (Alharthi et al, 2018(Alharthi et al, , 2019bZenobi et al, 2018).…”

“…From a physiological point of view, increased supply of FOA and cobalt, the latter by enhancing B 12 ruminal synthesis, could lead to greater endogenous Met synthesis (i.e., remethylation; Xue and Snoswell, 1985a,b). Although isolated effects of maternal supplementation with methyl donors during early postnatal life have already been demonstrated (Jacometo et al, 2016(Jacometo et al, , 2017(Jacometo et al, , 2018Abdelmegeid et al, 2017;Alharthi et al, 2018Alharthi et al, , 2019a, it remains to be determined whether increased supply of FOA and B 12 , through increased cobalt supply, alone or combined with Met, generate similar effects in neonatal innate immune responses.…”