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 productio...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.展开更多
Background： Feeding higher-energy prepartum is a common practice in the dairy industry. However, recent data underscore how it could reduce performance, deepen negative energy balance, and augment inflammation and ox...Background： Feeding higher-energy prepartum is a common practice in the dairy industry. However, recent data underscore how it could reduce performance, deepen negative energy balance, and augment inflammation and oxidative stress in fresh cows. We tested the effectiveness of rumen-protected methionine in preventing the negative effect of feeding a higher-energy prepartum. Multiparous Holstein cows were fed a control lower-energy diet（CON, 1.24 Mcal/kg DM; high-straw） during the whole dry period（-50 d）, or were switched to a higher-energy（OVE, 1.54 Mcal/kg DM）, or OVE plus Smartamine M（OVE ＋ SM; Adisseo NA） during the last 21 d before calving.Afterwards cows received the same lactation diet（1.75 Mcal/kg DM）. Smartamine M was top-dressed on the OVE diet（0.07% of DM） from -21 through 30 d in milk（DIM）. Liver samples were obtained via percutaneous biopsy at -10, 7 and 21 DIM. Expression of genes associated with energy and lipid metabolism, hepatokines, methionine cycle, antioxidant capacity and inflammation was measured.Results： Postpartal dry matter intake, milk yield, and energy-corrected milk were higher in CON and OVE ＋ SM compared with OVE. Furthermore, milk protein and fat percentages were greater in OVE ＋ SM compared with CON and OVE. Expression of the gluconeogenic gene PCK1 and the lipid-metabolism transcription regulator PPARA was again greater with CON and OVE ＋ SM compared with OVE. Expression of the lipoprotein synthesis enzyme MTTP was lower in OVE ＋ SM than CON or OVE. Similarly, the hepatokine FGF21, which correlates with severity of negative energy balance, was increased postpartum only in OVE compared to the other two groups. These results indicate greater liver metabolism and functions to support a greater production in OVE ＋ SM. At 7 DIM, the enzyme GSR involved in the synthesis of glutathione tended to be upregulated in OVE than CON-fed cows, suggesting a greater antioxidant demand in overfed cows. Feeding OVE ＋ SM resulted in lower similar expression of GSR compared with CON. Expression of the methionine cycle enzymes SAHH and MTR, both of which help synthesize methionine endogenously, was greater prepartum in OVE ＋ SM compared with both CON and OVE, and at 7 DIM for CON and OVE ＋ SM compared with OVE, suggesting greater Met availability. It is noteworthy that DNMT3A, which utilizes S-adenosylmethionine generated in the methionine cycle, was greater in OVE and OVE ＋ SM indicating higher-energy diets might enhance DNA methylation, thus, Met utilization.Conclusions： Data indicate that supplemental Smartamine M was able to compensate for the negative effect of prepartal energy-overfeeding by alleviating the demand for intracellular antioxidants, thus, contributing to the increase in production. Moreover Smartamine M improved hepatic lipid and glucose metabolism, leading to greater liver function and better overall health.展开更多
Background： G-protein coupled receptors（GPCR）, also referred as Free Fatty Acid Receptors（FFAR）, are widely studied within human medicine as drug targets for metabolic disorders. To combat metabolic disorders pre...Background： G-protein coupled receptors（GPCR）, also referred as Free Fatty Acid Receptors（FFAR）, are widely studied within human medicine as drug targets for metabolic disorders. To combat metabolic disorders prevalent in dairy cows during the transition period, which co-occur with negative energy balance and changes to lipid and glucose metabolism, it may be helpful to identify locations and roles of FFAR and other members of the GPCR family in bovine tissues.Results： Quantitative RT-PCR（qPCR） of subcutaneous adipose, liver, and PMNL samples during the transition period（-10, ＋7, and ＋20 or ＋30 d） were used for expression profiling of medium-（MCFA） and long-chain fatty acid（LCFA）receptors GPR120 and GPR40, MCFA receptor GPR84, and niacin receptor HCAR2/3. Adipose samples were obtained from cows with either high（HI; BCS ≥ 3.75） or low（LO; BCS ≤ 3.25） body condition score（BCS） to examine whether FFAR expression is correlated with this indicator of health and body reserves. Supplementation of rumen-protected methionine（MET）, which may improve immune function and production postpartum, was also compared with unsupplemented control（CON） cows for liver and blood polymorphonuclear leukocytes（PMNL） samples. In adipose tissue, GPR84 and GPR120 were differentially expressed over time, while GPR40 was not expressed; in PMNL, GPR40 was differentially expressed over time and between MET vs. CON, GPR84 expression differed only between dietary groups, and GPR120 was not expressed; in liver, GPCR were either not expressed or barely detectable.Conclusions： The data indicate that there is likely not a direct role in liver for the selected GPCR during the transition period, but they do play variable roles in adipose and PMN. In future, these receptors may prove useful targets and/or markers for peripartal metabolism and immunity.展开更多
文摘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.
基金Financial support for the research was provided in part by Adisseo(Commentry,France)Hatch funds under project ILLU-538–914,National Institute of Food and Agriculture,Washington,DC,USA
文摘Background： Feeding higher-energy prepartum is a common practice in the dairy industry. However, recent data underscore how it could reduce performance, deepen negative energy balance, and augment inflammation and oxidative stress in fresh cows. We tested the effectiveness of rumen-protected methionine in preventing the negative effect of feeding a higher-energy prepartum. Multiparous Holstein cows were fed a control lower-energy diet（CON, 1.24 Mcal/kg DM; high-straw） during the whole dry period（-50 d）, or were switched to a higher-energy（OVE, 1.54 Mcal/kg DM）, or OVE plus Smartamine M（OVE ＋ SM; Adisseo NA） during the last 21 d before calving.Afterwards cows received the same lactation diet（1.75 Mcal/kg DM）. Smartamine M was top-dressed on the OVE diet（0.07% of DM） from -21 through 30 d in milk（DIM）. Liver samples were obtained via percutaneous biopsy at -10, 7 and 21 DIM. Expression of genes associated with energy and lipid metabolism, hepatokines, methionine cycle, antioxidant capacity and inflammation was measured.Results： Postpartal dry matter intake, milk yield, and energy-corrected milk were higher in CON and OVE ＋ SM compared with OVE. Furthermore, milk protein and fat percentages were greater in OVE ＋ SM compared with CON and OVE. Expression of the gluconeogenic gene PCK1 and the lipid-metabolism transcription regulator PPARA was again greater with CON and OVE ＋ SM compared with OVE. Expression of the lipoprotein synthesis enzyme MTTP was lower in OVE ＋ SM than CON or OVE. Similarly, the hepatokine FGF21, which correlates with severity of negative energy balance, was increased postpartum only in OVE compared to the other two groups. These results indicate greater liver metabolism and functions to support a greater production in OVE ＋ SM. At 7 DIM, the enzyme GSR involved in the synthesis of glutathione tended to be upregulated in OVE than CON-fed cows, suggesting a greater antioxidant demand in overfed cows. Feeding OVE ＋ SM resulted in lower similar expression of GSR compared with CON. Expression of the methionine cycle enzymes SAHH and MTR, both of which help synthesize methionine endogenously, was greater prepartum in OVE ＋ SM compared with both CON and OVE, and at 7 DIM for CON and OVE ＋ SM compared with OVE, suggesting greater Met availability. It is noteworthy that DNMT3A, which utilizes S-adenosylmethionine generated in the methionine cycle, was greater in OVE and OVE ＋ SM indicating higher-energy diets might enhance DNA methylation, thus, Met utilization.Conclusions： Data indicate that supplemental Smartamine M was able to compensate for the negative effect of prepartal energy-overfeeding by alleviating the demand for intracellular antioxidants, thus, contributing to the increase in production. Moreover Smartamine M improved hepatic lipid and glucose metabolism, leading to greater liver function and better overall health.
基金Acknowledgements Alea Agrawal is a recipient of a Jonathan Baldwin Turner MS fellowship from the University of Illinois (Urbana-Champaign). Z. Zhou is recipient of a fellowship from China Scholarship Council (CSC) to perform his PhD studies at the University of Illinois (Urbana-Champaign). The funders had no role in the design of the study and collection, analysis, and interpretation of data and in writing of the manuscript.
文摘Background： G-protein coupled receptors（GPCR）, also referred as Free Fatty Acid Receptors（FFAR）, are widely studied within human medicine as drug targets for metabolic disorders. To combat metabolic disorders prevalent in dairy cows during the transition period, which co-occur with negative energy balance and changes to lipid and glucose metabolism, it may be helpful to identify locations and roles of FFAR and other members of the GPCR family in bovine tissues.Results： Quantitative RT-PCR（qPCR） of subcutaneous adipose, liver, and PMNL samples during the transition period（-10, ＋7, and ＋20 or ＋30 d） were used for expression profiling of medium-（MCFA） and long-chain fatty acid（LCFA）receptors GPR120 and GPR40, MCFA receptor GPR84, and niacin receptor HCAR2/3. Adipose samples were obtained from cows with either high（HI; BCS ≥ 3.75） or low（LO; BCS ≤ 3.25） body condition score（BCS） to examine whether FFAR expression is correlated with this indicator of health and body reserves. Supplementation of rumen-protected methionine（MET）, which may improve immune function and production postpartum, was also compared with unsupplemented control（CON） cows for liver and blood polymorphonuclear leukocytes（PMNL） samples. In adipose tissue, GPR84 and GPR120 were differentially expressed over time, while GPR40 was not expressed; in PMNL, GPR40 was differentially expressed over time and between MET vs. CON, GPR84 expression differed only between dietary groups, and GPR120 was not expressed; in liver, GPCR were either not expressed or barely detectable.Conclusions： The data indicate that there is likely not a direct role in liver for the selected GPCR during the transition period, but they do play variable roles in adipose and PMN. In future, these receptors may prove useful targets and/or markers for peripartal metabolism and immunity.
