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

Dairy cattle undergo dramatic metabolic, endocrine, physiologic and immune changes during the peripartal period largely due to combined increases in energy requirements for fetal growth and development, milk production, and decreased dry matter intake. The negative nutrient balance that develops results in body fat mobilization,subsequently leading to triacylglycerol(TAG) accumulation in the liver along with reductions in liver function,immune dysfunction and a state of inflammation and oxidative stress. Mobilization of muscle and gluconeogenesis are also enhanced, while intake of vitamins and minerals is decreased, contributing to metabolic and immune dysfunction and oxidative stress. Enhancing post-ruminal supply of methyl donors is one approach that may improve immunometabolism and production synergistically in peripartal cows. At the cellular level, methyl donors(e.g. methionine, choline, betaine and folic acid) interact through one-carbon metabolism to modulate metabolism,immune responses and epigenetic events. By modulating those pathways, methyl donors may help increase the export of very low-density lipoproteins to reduce liver TAG and contribute to antioxidant synthesis to alleviate oxidative stress. Thus, altering one-carbon metabolism through methyl donor supplementation is a viable option to modulate immunometabolism during the peripartal period. This review explores available data on the regulation of one-carbon metabolism pathways in dairy cows in the context of enzyme regulation, cellular sensors and signaling mechanisms that might respond to increased dietary supply of specific methyl donors. Effects of methyl donors beyond the one-carbon metabolism pathways, including production performance, immune cell function,mechanistic target or rapamycin signaling, and fatty acid oxidation will also be highlighted. Furthermore, the effects of body condition and feeding system(total mixed ration vs. pasture) on one-carbon metabolism pathways are explored. Potential effects of methyl donor supply during the pepartum period on dairy calf growth and development also are discussed. Lastly, practical nutritional recommendations related to methyl donor metabolism during the peripartal period are presented. Nutritional management during the peripartal period is a fertile area of research, hence, underscoring the importance for developing a systems understanding of the potential immunometabolic role that dietary methyl donors play during this period to promote health and performance.

Maternal supply of methionine during late-pregnancy enhances rate of Holstein calf development in utero and postnatal growth to a greater extent than colostrum source

Background: Pregnancy and early life are critical periods of plasticity during which the fetus and neonate may be influenced by environmental factors such as nutrition.Maternal methionine(Met) supply in non-ruminants during pregnancy can affect offspring development and growth.Thus,the objective of this study was to investigate if increasing Met supply during late-pregnancy affects developmental parameters of the calf at birth and if either maternal Met or colostrum from Met-fed cows alters calf growth.Calves born to Holstein cows individually-fed a basal control [CON; 1.47 Mcal/kg dry matter(DM) and 15.3% crude protein] diet with no added Met or CON plus ethylcellulose rumen-protected Met(MET; Mepron? at 0.09% of diet DM; Evonik Nutrition & Care GmbH,Germany)during the last 28 ± 2 d of pregnancy were used.A total of 39 calves were in CON(n = 22 bulls,17 heifers) and 42 in MET(n = 20 bulls,22 heifers).At birth,calves were randomly allocated considering dam treatment and colostrum as fol ows: 1) calves from CON cows and colostrum from CON cows(n = 21); 2) calves from CON cows and colostrum from MET cows(n = 18); 3) calves from MET cows and colostrum from MET cows(n = 22); and 4) calves from MET cows and colostrum from CON cows(n = 20).Al calves were housed,managed,and fed individual y during the first 9 wk of life.Results: Despite greater daily DM intake pre-partum in cows fed MET(15.7 vs.14.4 ± 0.12 kg/d,P < 0.05),colostrum quality and quantity were not affected by maternal diet.At birth,MET calves had greater(P ≤ 0.05) body weight(BW,44.1 vs.42.1 ± 0.70 kg),hip height(HH,81.3 vs.79.6 ± 0.53 cm) and wither height(WH,77.8 vs.75.9 ± 0.47 cm).In contrast,concentrations of His,Lys,and Asn in plasma were lower(P ≤ 0.05) in MET calves.Regardless of colostrum source,the greater BW,HH,and WH in MET calves at birth persisted through 9 wk of age resulting in average responses of + 3.1 kg BW,+ 1.9 cm HH,and + 1.8 cm WH compared with CON.Average daily gain during the 9 wk was(P < 0.05) 0.72 ± 0.02 kg/d in MET compared with 0.67 ± 0.02 kg/d in CON calves.Respiratory scores were normal and did not differ(P > 0.05) due to maternal Met supply or colostrum source.However,fecal scores tended to be lower(P ≤ 0.10) in MET calves regardless of colostrum source.Conclusions: Increasing the maternal supply of MET during late-pregnancy enhanced growth in utero as wel as during the pre-weaning and early post-weaning periods.Although the ～ 1 kg/d greater DM intake during the last 2–3 wk prior to parturition could explain a portion of the 2 kg extra body mass of MET calves at birth,other mechanisms potential y encompassing nutrient assimilation efficiency likely played a role.Assessing the exact mechanisms sensitive to supply of Met or total amino acid supply during the latter stages of growth in utero merit further research.