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J P Cant - One of the best experts on this subject based on the ideXlab platform.

  • Effects of jugular infused methionine, lysine, and histidine as a group or leucine and isoleucine as a group on production and metabolism in lactating dairy cows.
    Journal of dairy science, 2020
    Co-Authors: P.s. Yoder, J P Cant, X. Huang, Izabelle Auxiliadora Molina De Almeida Teixeira, Mark D. Hanigan
    Abstract:

    ABSTRACT Essential AA (EAA), particularly leucine, isoleucine, methionine, and histidine, possess signaling properties for promoting cellular anabolic metabolism, whereas methionine, lysine, and histidine are considered also to be substrate limiting AA. The objective of this study was to evaluate production responses to supplementation of 2 AA groups in a 2 × 2 factorial design. Eight cows (99 ± 18 days in Milk) were assigned to 4 jugular infusion treatments consisting of saline (CON), methionine plus lysine plus histidine (MKH), isoleucine plus leucine (IL), or MKH plus IL, in a replicated 4 × 4 Latin square design. Periods were 18 d in length, comprising 8 d of rest followed by 10 d of jugular infusion. Daily infusion amounts were 21 g of methionine, 38 g of lysine, 20 g of histidine, 50 g of leucine, and 22 g of isoleucine. Cows were ad libitum fed a common diet consisting of 15.2% crude Protein and 1.61 Mcal/kg NEL on a dry matter basis that was predicted to meet rumen degradable Protein requirements but was 15% deficient in metabolizable Protein. Milk and energy-corrected Milk Yields increased by 2.3 kg/d and 1.9 kg/d, respectively, with infused IL, and no change was observed for MKH. Milk Protein concentration increased by 0.13 percentage units for MKH, whereas Milk Protein Yield increased for both MKH and IL by 84 g/d and 64 g/d, respectively. The Milk Protein Yield increase for MKH+IL was 145 g/d versus CON. Gross feed efficiency tended to increase with IL infusion, and N efficiency tended to increase with MKH infusion. Aggregate arterial EAA concentrations less Met, Lys, and His declined by 7.2% in response to MKH infusion. Arterial EAA less Ile and Leu also declined by 6.2% in response to IL infusion. Net total AA (TAA) and EAA uptake by the udder tended to increase in response to MKH infusion, whereas mammary blood flow increased in response to IL infusion, but TAA and EAA net uptakes were unaffected. Apparent udder affinity increased for TAA and EAA less Met, Lys, and His in response to MKH infusion, whereas affinity for EAA less Ile and Leu increased for IL infusion. Venous Met and Leu concentrations increased by 192% and 35% from the MKH and IL infusions, respectively, compared with CON, which indicates that intracellular concentration of these EAA changed substantially. Increases in Milk Protein Yield were observed from 2 groups of amino acids independently and additively, which contradicts the single limiting amino acid theory that a single EAA will limit Milk Protein Yield.

  • Symposium review: Amino acid uptake by the mammary glands: Where does the control lie?
    Journal of dairy science, 2018
    Co-Authors: J P Cant, J.j.m. Kim, Scott R.l. Cieslar, John Doelman
    Abstract:

    ABSTRACT Milk Protein Yield responses to changes in the profile of essential amino acids absorbed by the gastrointestinal tract or circulating in blood plasma do not follow the classic limiting amino acid response, in part because of an ability of the mammary glands to modify their blood flow rate and net clearance of amino acids out of plasma. The hypothesis that mammary blood flow is locally regulated to maintain ATP balance accounts for observed changes in flow due to postruminal glucose, insulin, and essential amino acid (EAA) infusions. An additional hypothesis that net mammary uptakes of metabolites from blood are affected by perturbations in their respective arterial concentrations and the rate of mammary blood flow also appears to hold for the energy metabolites glucose, acetate, β-hydroxybutyrate, and fatty acids. However, net EAA uptakes by the mammary glands are poorly predicted by models considering arterial concentrations and blood flow rates only. Evidence points to intramammary Protein synthesis and secretion as the determinant of net EAA uptake. The intracellular signaling network anchored by the mechanistic target of rapamycin complex 1 stands as an excellent candidate to explain nutritional effects on Milk Protein synthesis because it integrates information on physiological and nutritional state to affect Protein synthesis and cell metabolism, growth, proliferation, and differentiation in many cell types. In mammary cells in vitro and in vivo, the mechanistic target of rapamycin complex 1, integrated stress response, and glycogen synthase kinase-3 networks that contribute to regulation of initiation of mRNA translation are responsive to acute changes in nutrient supply and EAA profile. However, after several days of postruminal infusion of balanced and imbalanced EAA profiles, these signaling networks do not appear to continue to account for changes in Milk Protein Yields. Gene expression evidence suggests that regulation of components of the unfolded Protein response that control biogenesis of the endoplasmic reticulum and differentiation of a secretory phenotype may contribute to effects of nutrition on Milk Protein Yield. Connections between early signaling events and their long-term consequences should be sought.

  • Maintenance of plasma branched-chain amino acid concentrations during glucose infusion directs essential amino acids to extra-mammary tissues in lactating dairy cows.
    Journal of dairy science, 2018
    Co-Authors: Richelle V. Curtis, J. Doelman, J.j.m. Kim, J P Cant
    Abstract:

    The objectives of this study were to investigate the effects of branched-chain AA (BCAA) supplementation when glucose is infused postruminally into lactating dairy cows consuming a diet low in crude Protein (CP) and to test the hypothesis that low BCAA concentrations are responsible for the poor stimulation of Milk Protein Yield by glucose. Twelve early-lactation Holstein cows were randomly assigned to 15% and 12% CP diets in a switchback design of 6-wk periods. Cows consuming the 12% CP diet received 96-h continuous jugular infusions of saline and 1 kg/d of glucose with 0, 75, or 150 g/d of BCAA in a Latin square sequence of treatments. Compared with saline, glucose infusion did not affect dry matter intake but increased Milk Yield by 2.2 kg/d and Milk Protein and lactose Yields by 63 and 151 g/d, respectively. Mammary plasma flow increased 36% during glucose infusion compared with saline infusion, possibly because of a 31% decrease in total acetate plus β-hydroxybutyrate concentrations. Circulating concentrations of total essential AA and BCAA decreased 19 and 31%, respectively, during infusion of glucose, yet net mammary uptakes of AA remained unchanged compared with saline infusion. The addition of 75 and 150 g/d of BCAA to glucose infusions increased arterial concentrations of BCAA to 106 and 149%, respectively, of the concentrations in saline-infused cows, but caused a decrease in concentrations of non-branched-chain essential AA in plasma, as well as their mammary uptakes and Milk Protein Yields. Plasma urea concentration was not affected by BCAA infusion, indicating no change in catabolism of AA. The lack of mammary and catabolic effects leads us to suggest that BCAA exerted their effects on plasma concentrations of the other essential AA by stimulating utilization in skeletal muscle for Protein accretion. Results indicate that the glucose effect on Milk Protein Yield was not limited by low BCAA concentrations, and that a stimulation of extra-mammary use of non-branched-chain essential amino acids by BCAA led to a decrease in Milk Protein Yield.

  • Addition of glycerol to lactating cow diets stimulates dry matter intake and Milk Protein Yield to a greater extent than addition of corn grain
    Journal of dairy science, 2017
    Co-Authors: D.l. Bajramaj, R.v. Curtis, J.j.m. Kim, Milena Corredig, J. Doelman, T.c. Wright, V.r. Osborne, J P Cant
    Abstract:

    The objective of this study was to determine if the addition of glycerol to the diet of dairy cows would stimulate Milk Protein Yield in the same manner as the addition of corn grain. Twelve multiparous lactating dairy cows at 81 ± 5 d in Milk were subjected to 3 dietary treatments in a replicated 3 × 3 Latin square design for 28-d periods. The diets were a 70% forage diet considered the basal diet, the basal diet with 19% ground and high-moisture corn replacing forages, and the basal diet with 15% refined glycerol and 4% added Protein supplements to be isocaloric and isonitrogenous with the corn diet. Cows were Milked twice a day and samples were collected on the last 7 d of each period for compositional analysis. Within each period, blood samples were collected on d 26 and 27, and mammary tissue was collected by biopsy on d 28 for Western blot analysis. Dry matter intake increased from 23.7 kg/d on the basal diet to 25.8 kg/d on the corn diet and 27.2 kg/d on the glycerol diet. Dry matter intake tended to be higher with glycerol than corn. Milk production increased from 39.2 kg/d on the basal diet to 43.8 kg/d on the corn diet and 44.2 kg/d on the glycerol diet. However, Milk Yield did not differ between corn and glycerol diets. Milk lactose Yields were higher on the corn and glycerol diets than the basal diet. Milk fat Yield significantly decreased on the glycerol diet compared with the basal diet and tended to decrease in comparison with the corn diet. Mean Milk fat globule size was reduced by glycerol feeding. Milk Protein Yield increased 197 g/d with addition of corn to the basal diet and 263 g/d with addition of glycerol, and the glycerol effect was larger than the corn effect. The dietary treatments had no effects on plasma glucose concentration, but plasma acetate levels decreased 27% on the glycerol diet. Amino acid concentrations were not affected by dietary treatments, except for branched-chain amino acids, which decreased 22% on the glycerol diet compared with the corn diet. The decreases in plasma acetate and branched-chain amino acid concentrations with glycerol and the larger effects of glycerol than corn on Milk Protein and fat Yields suggest that glycerol is more glucogenic for cows than corn grain.

  • Exogenous essential amino acids stimulate an adaptive unfolded Protein response in the mammary glands of lactating cows.
    Journal of dairy science, 2017
    Co-Authors: K. Nichols, Michelle Carson, J.j.m. Kim, J.a. Metcalf, J. Doelman, J P Cant
    Abstract:

    The phosphorylation of mammalian target of rapamycin complex 1 (mTORC1) components and integrated stress response networks in the mammary glands of lactating cows have not accounted for the stimulation of Milk Protein Yield by chronic supplementation with AA or glucose. Faster Milk Protein synthesis could be a consequence of increased Milk Protein mRNA per cell, the number of ribosomes per cell, the secretory capacity of cells, or the mammary cell number. To investigate these 4 possibilities using a translational and transcriptional approach, we performed Protein and gene expression analyses of mammary and longissimus dorsi tissue collected from lactating dairy cows after 5 d of abomasal infusion with saline or 844 or 1,126 g/d of an essential AA (EAA) mixture, with and without 1,000 g/d glucose. Infusion with EAA increased Milk Protein Yield but did not affect the phosphorylation of mTORC1-related Proteins in the mammary gland. In skeletal muscle, phosphorylation of 4EBP1 (eIF4E-binding Protein 1) increased in response to both EAA and glucose, and phosphorylated S6K1 (70-kDa ribosomal Protein S6 kinase) increased with glucose. In response to EAA, mammary mRNA expression of the marker genes for Milk Proteins, ribosome biogenesis, and cell proliferation were not upregulated. Instead, reciprocal regulation of 2 arms of the unfolded Protein response occurred. Infusion of EAA for 5 d activated XBP1 (X-box binding Protein 1) mRNA, encoding a transcription factor for endoplasmic reticulum biogenesis, and it decreased the mRNA expression of genes encoding pro-apoptotic Protein CHOP (C/EBP homologous Protein) and downstream GADD34 (growth arrest and DNA damage-inducible 34). These findings implicate non-stress-related, adaptive capabilities of the unfolded Protein response in the long-term nutritional regulation of Milk Protein Yield in lactating dairy cows.

J.a. Metcalf - One of the best experts on this subject based on the ideXlab platform.

  • Exogenous essential amino acids stimulate an adaptive unfolded Protein response in the mammary glands of lactating cows.
    Journal of dairy science, 2017
    Co-Authors: K. Nichols, Michelle Carson, J.j.m. Kim, J.a. Metcalf, J. Doelman, J P Cant
    Abstract:

    The phosphorylation of mammalian target of rapamycin complex 1 (mTORC1) components and integrated stress response networks in the mammary glands of lactating cows have not accounted for the stimulation of Milk Protein Yield by chronic supplementation with AA or glucose. Faster Milk Protein synthesis could be a consequence of increased Milk Protein mRNA per cell, the number of ribosomes per cell, the secretory capacity of cells, or the mammary cell number. To investigate these 4 possibilities using a translational and transcriptional approach, we performed Protein and gene expression analyses of mammary and longissimus dorsi tissue collected from lactating dairy cows after 5 d of abomasal infusion with saline or 844 or 1,126 g/d of an essential AA (EAA) mixture, with and without 1,000 g/d glucose. Infusion with EAA increased Milk Protein Yield but did not affect the phosphorylation of mTORC1-related Proteins in the mammary gland. In skeletal muscle, phosphorylation of 4EBP1 (eIF4E-binding Protein 1) increased in response to both EAA and glucose, and phosphorylated S6K1 (70-kDa ribosomal Protein S6 kinase) increased with glucose. In response to EAA, mammary mRNA expression of the marker genes for Milk Proteins, ribosome biogenesis, and cell proliferation were not upregulated. Instead, reciprocal regulation of 2 arms of the unfolded Protein response occurred. Infusion of EAA for 5 d activated XBP1 (X-box binding Protein 1) mRNA, encoding a transcription factor for endoplasmic reticulum biogenesis, and it decreased the mRNA expression of genes encoding pro-apoptotic Protein CHOP (C/EBP homologous Protein) and downstream GADD34 (growth arrest and DNA damage-inducible 34). These findings implicate non-stress-related, adaptive capabilities of the unfolded Protein response in the long-term nutritional regulation of Milk Protein Yield in lactating dairy cows.

  • Branched-chain amino acid and lysine deficiencies exert different effects on mammary translational regulation
    Journal of dairy science, 2015
    Co-Authors: J. Doelman, J.j.m. Kim, Michelle Carson, J.a. Metcalf, J P Cant
    Abstract:

    Deficiencies and imbalances of specific group II essential amino acids (EAA) were created in lactating cows by an infusion subtraction protocol to explore effects on Milk production and abundance and phosphorylation state of regulators of mRNA translation in the mammary glands. Five lactating cows on a diet of 11.2% crude Protein were infused abomasally for 5d with saline, 563 g/d of a complete EAA mix, or EAA mixes without the branched-chain amino acids (BCAA), Leu, or Lys in a 5 × 5 Latin square design. Milk Protein Yield was stimulated by EAA infusion and returned to saline levels upon subtraction of BCAA, Leu, or Lys. Mammary abundance of phosphorylated S6K1 was measured as an indicator of mammalian target of rapamycin complex 1 (mTORC1) activity and was found not to be affected by the complete EAA mix but was increased by the mixture lacking Lys. Total S6K1 abundances in mammary tissue were elevated by complete and BCAA-lacking infusions. All of the EAA treatments except the one lacking BCAA upregulated mammary eIF2Be and eIF2α abundances, which is stimulatory to global mRNA translation. Phosphorylation state of eIF2Be tended to decrease when complete or Lys-lacking EAA mixtures were infused. Phosphorylation state of eIF2α was not affected by treatment. We detected a correlation of 0.62 between phosphorylation state of S6K1 and total eIF2Be abundance, and a correlation of 0.58 between phosphorylation state of S6K1 and total eIF2α abundance, suggesting that mTORC1 activation may have upregulated eIF2Be and eIF2α expression. Despite maintenance of mammary eIF2Be and eIF2α abundances during Leu and Lys deficiencies, Milk Protein Yield declined, suggesting that other factors are responsible for mediating effects of Lys and Leu. A deficiency of all 3 BCAA may impair Milk Protein Yield through deactivation of mTORC1-mediated upregulation of eIF2Be and eIF2α abundances.

  • essential amino acid infusions stimulate mammary expression of eukaryotic initiation factor 2be but Milk Protein Yield is not increased during an imbalance
    Journal of Dairy Science, 2015
    Co-Authors: John Doelman, R.v. Curtis, Michelle Carson, J.j.m. Kim, J.a. Metcalf, J P Cant
    Abstract:

    Abstract Essential amino acid (EAA) deficiencies and imbalances were created in lactating cows by using an infusion subtraction protocol to explore effects on Milk Protein Yield and activity state of regulators of mRNA translation in the mammary glands. Six lactating cows on a diet of 11.2% Protein were infused abomasally for 5 d with saline, 563 g/d of a complete EAA mix, or EAA without His, Met, Phe, or Trp in a 6 × 6 Latin square design. Infusion of complete and imbalanced EAA solutions increased mammalian target of rapamycin (mTOR) signaling in the mammary glands, as evidenced by higher ribosomal S6 kinase 1 (S6K1) phosphorylation compared with saline infusion. Total S6K1 abundance was decreased by imbalanced AA infusions. Except for the mixture lacking Phe, infusion of EAA, whether imbalanced or not, increased abundance of total eukaryotic initiation factor 2Be (eIF2Be). A correlation of 0.33 between phosphorylation state of S6K1 and total eIF2Be abundance suggests that an mTOR-mediated upregulation of eIF2Be translation occurred. Despite increased mTOR/eIF2Be signaling, Milk Protein Yields increased only with the complete EAA mixture compared with saline. Low plasma concentrations of His, Met, and Phe during their respective imbalances likely interfered with Protein synthesis. Total abundance and phosphorylation state of eukaryotic initiation factor 2α were not responsible for the interference. Further study of eIF2Be as a regulator of Milk Protein Yield is warranted.

  • Essential amino acid infusions stimulate mammary expression of eukaryotic initiation factor 2Bε but Milk Protein Yield is not increased during an imbalance
    Journal of dairy science, 2015
    Co-Authors: John Doelman, R.v. Curtis, Michelle Carson, J.j.m. Kim, J.a. Metcalf, J P Cant
    Abstract:

    Abstract Essential amino acid (EAA) deficiencies and imbalances were created in lactating cows by using an infusion subtraction protocol to explore effects on Milk Protein Yield and activity state of regulators of mRNA translation in the mammary glands. Six lactating cows on a diet of 11.2% Protein were infused abomasally for 5 d with saline, 563 g/d of a complete EAA mix, or EAA without His, Met, Phe, or Trp in a 6 × 6 Latin square design. Infusion of complete and imbalanced EAA solutions increased mammalian target of rapamycin (mTOR) signaling in the mammary glands, as evidenced by higher ribosomal S6 kinase 1 (S6K1) phosphorylation compared with saline infusion. Total S6K1 abundance was decreased by imbalanced AA infusions. Except for the mixture lacking Phe, infusion of EAA, whether imbalanced or not, increased abundance of total eukaryotic initiation factor 2Be (eIF2Be). A correlation of 0.33 between phosphorylation state of S6K1 and total eIF2Be abundance suggests that an mTOR-mediated upregulation of eIF2Be translation occurred. Despite increased mTOR/eIF2Be signaling, Milk Protein Yields increased only with the complete EAA mixture compared with saline. Low plasma concentrations of His, Met, and Phe during their respective imbalances likely interfered with Protein synthesis. Total abundance and phosphorylation state of eukaryotic initiation factor 2α were not responsible for the interference. Further study of eIF2Be as a regulator of Milk Protein Yield is warranted.

  • The Effect of Dietary Crude Protein as Protected Soybean Meal on Mammary Metabolism in the Lactating Dairy Cow
    Journal of dairy science, 1996
    Co-Authors: J.a. Metcalf, D. Wray-cahen, E.e. Chettle, J.d. Sutton, D.e. Beever, Les A. Crompton, John C. Macrae, Brian J. Bequette, F.r.c. Backwell
    Abstract:

    Metabolism in the mammary gland was related to changes in Milk output in response to changes in dietary Protein intake. Three diets of grass silage and concentrate were fed to four lactating dairy cows equipped with intravascular catheters across the mammary gland. Concentrates differed in the inclusion of protected soybean meal and provided 11.3, 15.4, and 20.1% CP, respectively. Blood samples were taken to assess the effect of Protein percentage on the nutrient fluxes across the gland and their relationship to Milk production. Milk production, Milk Protein Yield, and Milk Protein concentration were all increased as CP intake increased, although these responses were not linear. Concentrations of urea in Milk reflected those in plasma and increased as dietary Protein intake increased. Uptake of glucose and BHBA by the mammary gland tended to increase as Milk production increased. Arterial supply of essential AA increased as the dietary Protein increased. Supply and uptake of nonessential AA were unchanged by dietary treatment, and uptake was insufficient to account for output of nonessential AA residues in Milk Protein. The supply of essential AA was not limiting for Milk Protein synthesis, and some alternative mechanism must have existed for the control of Milk Protein Yield.

J.j.m. Kim - One of the best experts on this subject based on the ideXlab platform.

  • Symposium review: Amino acid uptake by the mammary glands: Where does the control lie?
    Journal of dairy science, 2018
    Co-Authors: J P Cant, J.j.m. Kim, Scott R.l. Cieslar, John Doelman
    Abstract:

    ABSTRACT Milk Protein Yield responses to changes in the profile of essential amino acids absorbed by the gastrointestinal tract or circulating in blood plasma do not follow the classic limiting amino acid response, in part because of an ability of the mammary glands to modify their blood flow rate and net clearance of amino acids out of plasma. The hypothesis that mammary blood flow is locally regulated to maintain ATP balance accounts for observed changes in flow due to postruminal glucose, insulin, and essential amino acid (EAA) infusions. An additional hypothesis that net mammary uptakes of metabolites from blood are affected by perturbations in their respective arterial concentrations and the rate of mammary blood flow also appears to hold for the energy metabolites glucose, acetate, β-hydroxybutyrate, and fatty acids. However, net EAA uptakes by the mammary glands are poorly predicted by models considering arterial concentrations and blood flow rates only. Evidence points to intramammary Protein synthesis and secretion as the determinant of net EAA uptake. The intracellular signaling network anchored by the mechanistic target of rapamycin complex 1 stands as an excellent candidate to explain nutritional effects on Milk Protein synthesis because it integrates information on physiological and nutritional state to affect Protein synthesis and cell metabolism, growth, proliferation, and differentiation in many cell types. In mammary cells in vitro and in vivo, the mechanistic target of rapamycin complex 1, integrated stress response, and glycogen synthase kinase-3 networks that contribute to regulation of initiation of mRNA translation are responsive to acute changes in nutrient supply and EAA profile. However, after several days of postruminal infusion of balanced and imbalanced EAA profiles, these signaling networks do not appear to continue to account for changes in Milk Protein Yields. Gene expression evidence suggests that regulation of components of the unfolded Protein response that control biogenesis of the endoplasmic reticulum and differentiation of a secretory phenotype may contribute to effects of nutrition on Milk Protein Yield. Connections between early signaling events and their long-term consequences should be sought.

  • Maintenance of plasma branched-chain amino acid concentrations during glucose infusion directs essential amino acids to extra-mammary tissues in lactating dairy cows.
    Journal of dairy science, 2018
    Co-Authors: Richelle V. Curtis, J. Doelman, J.j.m. Kim, J P Cant
    Abstract:

    The objectives of this study were to investigate the effects of branched-chain AA (BCAA) supplementation when glucose is infused postruminally into lactating dairy cows consuming a diet low in crude Protein (CP) and to test the hypothesis that low BCAA concentrations are responsible for the poor stimulation of Milk Protein Yield by glucose. Twelve early-lactation Holstein cows were randomly assigned to 15% and 12% CP diets in a switchback design of 6-wk periods. Cows consuming the 12% CP diet received 96-h continuous jugular infusions of saline and 1 kg/d of glucose with 0, 75, or 150 g/d of BCAA in a Latin square sequence of treatments. Compared with saline, glucose infusion did not affect dry matter intake but increased Milk Yield by 2.2 kg/d and Milk Protein and lactose Yields by 63 and 151 g/d, respectively. Mammary plasma flow increased 36% during glucose infusion compared with saline infusion, possibly because of a 31% decrease in total acetate plus β-hydroxybutyrate concentrations. Circulating concentrations of total essential AA and BCAA decreased 19 and 31%, respectively, during infusion of glucose, yet net mammary uptakes of AA remained unchanged compared with saline infusion. The addition of 75 and 150 g/d of BCAA to glucose infusions increased arterial concentrations of BCAA to 106 and 149%, respectively, of the concentrations in saline-infused cows, but caused a decrease in concentrations of non-branched-chain essential AA in plasma, as well as their mammary uptakes and Milk Protein Yields. Plasma urea concentration was not affected by BCAA infusion, indicating no change in catabolism of AA. The lack of mammary and catabolic effects leads us to suggest that BCAA exerted their effects on plasma concentrations of the other essential AA by stimulating utilization in skeletal muscle for Protein accretion. Results indicate that the glucose effect on Milk Protein Yield was not limited by low BCAA concentrations, and that a stimulation of extra-mammary use of non-branched-chain essential amino acids by BCAA led to a decrease in Milk Protein Yield.

  • Addition of glycerol to lactating cow diets stimulates dry matter intake and Milk Protein Yield to a greater extent than addition of corn grain
    Journal of dairy science, 2017
    Co-Authors: D.l. Bajramaj, R.v. Curtis, J.j.m. Kim, Milena Corredig, J. Doelman, T.c. Wright, V.r. Osborne, J P Cant
    Abstract:

    The objective of this study was to determine if the addition of glycerol to the diet of dairy cows would stimulate Milk Protein Yield in the same manner as the addition of corn grain. Twelve multiparous lactating dairy cows at 81 ± 5 d in Milk were subjected to 3 dietary treatments in a replicated 3 × 3 Latin square design for 28-d periods. The diets were a 70% forage diet considered the basal diet, the basal diet with 19% ground and high-moisture corn replacing forages, and the basal diet with 15% refined glycerol and 4% added Protein supplements to be isocaloric and isonitrogenous with the corn diet. Cows were Milked twice a day and samples were collected on the last 7 d of each period for compositional analysis. Within each period, blood samples were collected on d 26 and 27, and mammary tissue was collected by biopsy on d 28 for Western blot analysis. Dry matter intake increased from 23.7 kg/d on the basal diet to 25.8 kg/d on the corn diet and 27.2 kg/d on the glycerol diet. Dry matter intake tended to be higher with glycerol than corn. Milk production increased from 39.2 kg/d on the basal diet to 43.8 kg/d on the corn diet and 44.2 kg/d on the glycerol diet. However, Milk Yield did not differ between corn and glycerol diets. Milk lactose Yields were higher on the corn and glycerol diets than the basal diet. Milk fat Yield significantly decreased on the glycerol diet compared with the basal diet and tended to decrease in comparison with the corn diet. Mean Milk fat globule size was reduced by glycerol feeding. Milk Protein Yield increased 197 g/d with addition of corn to the basal diet and 263 g/d with addition of glycerol, and the glycerol effect was larger than the corn effect. The dietary treatments had no effects on plasma glucose concentration, but plasma acetate levels decreased 27% on the glycerol diet. Amino acid concentrations were not affected by dietary treatments, except for branched-chain amino acids, which decreased 22% on the glycerol diet compared with the corn diet. The decreases in plasma acetate and branched-chain amino acid concentrations with glycerol and the larger effects of glycerol than corn on Milk Protein and fat Yields suggest that glycerol is more glucogenic for cows than corn grain.

  • Exogenous essential amino acids stimulate an adaptive unfolded Protein response in the mammary glands of lactating cows.
    Journal of dairy science, 2017
    Co-Authors: K. Nichols, Michelle Carson, J.j.m. Kim, J.a. Metcalf, J. Doelman, J P Cant
    Abstract:

    The phosphorylation of mammalian target of rapamycin complex 1 (mTORC1) components and integrated stress response networks in the mammary glands of lactating cows have not accounted for the stimulation of Milk Protein Yield by chronic supplementation with AA or glucose. Faster Milk Protein synthesis could be a consequence of increased Milk Protein mRNA per cell, the number of ribosomes per cell, the secretory capacity of cells, or the mammary cell number. To investigate these 4 possibilities using a translational and transcriptional approach, we performed Protein and gene expression analyses of mammary and longissimus dorsi tissue collected from lactating dairy cows after 5 d of abomasal infusion with saline or 844 or 1,126 g/d of an essential AA (EAA) mixture, with and without 1,000 g/d glucose. Infusion with EAA increased Milk Protein Yield but did not affect the phosphorylation of mTORC1-related Proteins in the mammary gland. In skeletal muscle, phosphorylation of 4EBP1 (eIF4E-binding Protein 1) increased in response to both EAA and glucose, and phosphorylated S6K1 (70-kDa ribosomal Protein S6 kinase) increased with glucose. In response to EAA, mammary mRNA expression of the marker genes for Milk Proteins, ribosome biogenesis, and cell proliferation were not upregulated. Instead, reciprocal regulation of 2 arms of the unfolded Protein response occurred. Infusion of EAA for 5 d activated XBP1 (X-box binding Protein 1) mRNA, encoding a transcription factor for endoplasmic reticulum biogenesis, and it decreased the mRNA expression of genes encoding pro-apoptotic Protein CHOP (C/EBP homologous Protein) and downstream GADD34 (growth arrest and DNA damage-inducible 34). These findings implicate non-stress-related, adaptive capabilities of the unfolded Protein response in the long-term nutritional regulation of Milk Protein Yield in lactating dairy cows.

  • Branched-chain amino acid and lysine deficiencies exert different effects on mammary translational regulation
    Journal of dairy science, 2015
    Co-Authors: J. Doelman, J.j.m. Kim, Michelle Carson, J.a. Metcalf, J P Cant
    Abstract:

    Deficiencies and imbalances of specific group II essential amino acids (EAA) were created in lactating cows by an infusion subtraction protocol to explore effects on Milk production and abundance and phosphorylation state of regulators of mRNA translation in the mammary glands. Five lactating cows on a diet of 11.2% crude Protein were infused abomasally for 5d with saline, 563 g/d of a complete EAA mix, or EAA mixes without the branched-chain amino acids (BCAA), Leu, or Lys in a 5 × 5 Latin square design. Milk Protein Yield was stimulated by EAA infusion and returned to saline levels upon subtraction of BCAA, Leu, or Lys. Mammary abundance of phosphorylated S6K1 was measured as an indicator of mammalian target of rapamycin complex 1 (mTORC1) activity and was found not to be affected by the complete EAA mix but was increased by the mixture lacking Lys. Total S6K1 abundances in mammary tissue were elevated by complete and BCAA-lacking infusions. All of the EAA treatments except the one lacking BCAA upregulated mammary eIF2Be and eIF2α abundances, which is stimulatory to global mRNA translation. Phosphorylation state of eIF2Be tended to decrease when complete or Lys-lacking EAA mixtures were infused. Phosphorylation state of eIF2α was not affected by treatment. We detected a correlation of 0.62 between phosphorylation state of S6K1 and total eIF2Be abundance, and a correlation of 0.58 between phosphorylation state of S6K1 and total eIF2α abundance, suggesting that mTORC1 activation may have upregulated eIF2Be and eIF2α expression. Despite maintenance of mammary eIF2Be and eIF2α abundances during Leu and Lys deficiencies, Milk Protein Yield declined, suggesting that other factors are responsible for mediating effects of Lys and Leu. A deficiency of all 3 BCAA may impair Milk Protein Yield through deactivation of mTORC1-mediated upregulation of eIF2Be and eIF2α abundances.

John Doelman - One of the best experts on this subject based on the ideXlab platform.

  • Symposium review: Amino acid uptake by the mammary glands: Where does the control lie?
    Journal of dairy science, 2018
    Co-Authors: J P Cant, J.j.m. Kim, Scott R.l. Cieslar, John Doelman
    Abstract:

    ABSTRACT Milk Protein Yield responses to changes in the profile of essential amino acids absorbed by the gastrointestinal tract or circulating in blood plasma do not follow the classic limiting amino acid response, in part because of an ability of the mammary glands to modify their blood flow rate and net clearance of amino acids out of plasma. The hypothesis that mammary blood flow is locally regulated to maintain ATP balance accounts for observed changes in flow due to postruminal glucose, insulin, and essential amino acid (EAA) infusions. An additional hypothesis that net mammary uptakes of metabolites from blood are affected by perturbations in their respective arterial concentrations and the rate of mammary blood flow also appears to hold for the energy metabolites glucose, acetate, β-hydroxybutyrate, and fatty acids. However, net EAA uptakes by the mammary glands are poorly predicted by models considering arterial concentrations and blood flow rates only. Evidence points to intramammary Protein synthesis and secretion as the determinant of net EAA uptake. The intracellular signaling network anchored by the mechanistic target of rapamycin complex 1 stands as an excellent candidate to explain nutritional effects on Milk Protein synthesis because it integrates information on physiological and nutritional state to affect Protein synthesis and cell metabolism, growth, proliferation, and differentiation in many cell types. In mammary cells in vitro and in vivo, the mechanistic target of rapamycin complex 1, integrated stress response, and glycogen synthase kinase-3 networks that contribute to regulation of initiation of mRNA translation are responsive to acute changes in nutrient supply and EAA profile. However, after several days of postruminal infusion of balanced and imbalanced EAA profiles, these signaling networks do not appear to continue to account for changes in Milk Protein Yields. Gene expression evidence suggests that regulation of components of the unfolded Protein response that control biogenesis of the endoplasmic reticulum and differentiation of a secretory phenotype may contribute to effects of nutrition on Milk Protein Yield. Connections between early signaling events and their long-term consequences should be sought.

  • essential amino acid infusions stimulate mammary expression of eukaryotic initiation factor 2be but Milk Protein Yield is not increased during an imbalance
    Journal of Dairy Science, 2015
    Co-Authors: John Doelman, R.v. Curtis, Michelle Carson, J.j.m. Kim, J.a. Metcalf, J P Cant
    Abstract:

    Abstract Essential amino acid (EAA) deficiencies and imbalances were created in lactating cows by using an infusion subtraction protocol to explore effects on Milk Protein Yield and activity state of regulators of mRNA translation in the mammary glands. Six lactating cows on a diet of 11.2% Protein were infused abomasally for 5 d with saline, 563 g/d of a complete EAA mix, or EAA without His, Met, Phe, or Trp in a 6 × 6 Latin square design. Infusion of complete and imbalanced EAA solutions increased mammalian target of rapamycin (mTOR) signaling in the mammary glands, as evidenced by higher ribosomal S6 kinase 1 (S6K1) phosphorylation compared with saline infusion. Total S6K1 abundance was decreased by imbalanced AA infusions. Except for the mixture lacking Phe, infusion of EAA, whether imbalanced or not, increased abundance of total eukaryotic initiation factor 2Be (eIF2Be). A correlation of 0.33 between phosphorylation state of S6K1 and total eIF2Be abundance suggests that an mTOR-mediated upregulation of eIF2Be translation occurred. Despite increased mTOR/eIF2Be signaling, Milk Protein Yields increased only with the complete EAA mixture compared with saline. Low plasma concentrations of His, Met, and Phe during their respective imbalances likely interfered with Protein synthesis. Total abundance and phosphorylation state of eukaryotic initiation factor 2α were not responsible for the interference. Further study of eIF2Be as a regulator of Milk Protein Yield is warranted.

  • Essential amino acid infusions stimulate mammary expression of eukaryotic initiation factor 2Bε but Milk Protein Yield is not increased during an imbalance
    Journal of dairy science, 2015
    Co-Authors: John Doelman, R.v. Curtis, Michelle Carson, J.j.m. Kim, J.a. Metcalf, J P Cant
    Abstract:

    Abstract Essential amino acid (EAA) deficiencies and imbalances were created in lactating cows by using an infusion subtraction protocol to explore effects on Milk Protein Yield and activity state of regulators of mRNA translation in the mammary glands. Six lactating cows on a diet of 11.2% Protein were infused abomasally for 5 d with saline, 563 g/d of a complete EAA mix, or EAA without His, Met, Phe, or Trp in a 6 × 6 Latin square design. Infusion of complete and imbalanced EAA solutions increased mammalian target of rapamycin (mTOR) signaling in the mammary glands, as evidenced by higher ribosomal S6 kinase 1 (S6K1) phosphorylation compared with saline infusion. Total S6K1 abundance was decreased by imbalanced AA infusions. Except for the mixture lacking Phe, infusion of EAA, whether imbalanced or not, increased abundance of total eukaryotic initiation factor 2Be (eIF2Be). A correlation of 0.33 between phosphorylation state of S6K1 and total eIF2Be abundance suggests that an mTOR-mediated upregulation of eIF2Be translation occurred. Despite increased mTOR/eIF2Be signaling, Milk Protein Yields increased only with the complete EAA mixture compared with saline. Low plasma concentrations of His, Met, and Phe during their respective imbalances likely interfered with Protein synthesis. Total abundance and phosphorylation state of eukaryotic initiation factor 2α were not responsible for the interference. Further study of eIF2Be as a regulator of Milk Protein Yield is warranted.

Michelle Carson - One of the best experts on this subject based on the ideXlab platform.

  • Exogenous essential amino acids stimulate an adaptive unfolded Protein response in the mammary glands of lactating cows.
    Journal of dairy science, 2017
    Co-Authors: K. Nichols, Michelle Carson, J.j.m. Kim, J.a. Metcalf, J. Doelman, J P Cant
    Abstract:

    The phosphorylation of mammalian target of rapamycin complex 1 (mTORC1) components and integrated stress response networks in the mammary glands of lactating cows have not accounted for the stimulation of Milk Protein Yield by chronic supplementation with AA or glucose. Faster Milk Protein synthesis could be a consequence of increased Milk Protein mRNA per cell, the number of ribosomes per cell, the secretory capacity of cells, or the mammary cell number. To investigate these 4 possibilities using a translational and transcriptional approach, we performed Protein and gene expression analyses of mammary and longissimus dorsi tissue collected from lactating dairy cows after 5 d of abomasal infusion with saline or 844 or 1,126 g/d of an essential AA (EAA) mixture, with and without 1,000 g/d glucose. Infusion with EAA increased Milk Protein Yield but did not affect the phosphorylation of mTORC1-related Proteins in the mammary gland. In skeletal muscle, phosphorylation of 4EBP1 (eIF4E-binding Protein 1) increased in response to both EAA and glucose, and phosphorylated S6K1 (70-kDa ribosomal Protein S6 kinase) increased with glucose. In response to EAA, mammary mRNA expression of the marker genes for Milk Proteins, ribosome biogenesis, and cell proliferation were not upregulated. Instead, reciprocal regulation of 2 arms of the unfolded Protein response occurred. Infusion of EAA for 5 d activated XBP1 (X-box binding Protein 1) mRNA, encoding a transcription factor for endoplasmic reticulum biogenesis, and it decreased the mRNA expression of genes encoding pro-apoptotic Protein CHOP (C/EBP homologous Protein) and downstream GADD34 (growth arrest and DNA damage-inducible 34). These findings implicate non-stress-related, adaptive capabilities of the unfolded Protein response in the long-term nutritional regulation of Milk Protein Yield in lactating dairy cows.

  • Branched-chain amino acid and lysine deficiencies exert different effects on mammary translational regulation
    Journal of dairy science, 2015
    Co-Authors: J. Doelman, J.j.m. Kim, Michelle Carson, J.a. Metcalf, J P Cant
    Abstract:

    Deficiencies and imbalances of specific group II essential amino acids (EAA) were created in lactating cows by an infusion subtraction protocol to explore effects on Milk production and abundance and phosphorylation state of regulators of mRNA translation in the mammary glands. Five lactating cows on a diet of 11.2% crude Protein were infused abomasally for 5d with saline, 563 g/d of a complete EAA mix, or EAA mixes without the branched-chain amino acids (BCAA), Leu, or Lys in a 5 × 5 Latin square design. Milk Protein Yield was stimulated by EAA infusion and returned to saline levels upon subtraction of BCAA, Leu, or Lys. Mammary abundance of phosphorylated S6K1 was measured as an indicator of mammalian target of rapamycin complex 1 (mTORC1) activity and was found not to be affected by the complete EAA mix but was increased by the mixture lacking Lys. Total S6K1 abundances in mammary tissue were elevated by complete and BCAA-lacking infusions. All of the EAA treatments except the one lacking BCAA upregulated mammary eIF2Be and eIF2α abundances, which is stimulatory to global mRNA translation. Phosphorylation state of eIF2Be tended to decrease when complete or Lys-lacking EAA mixtures were infused. Phosphorylation state of eIF2α was not affected by treatment. We detected a correlation of 0.62 between phosphorylation state of S6K1 and total eIF2Be abundance, and a correlation of 0.58 between phosphorylation state of S6K1 and total eIF2α abundance, suggesting that mTORC1 activation may have upregulated eIF2Be and eIF2α expression. Despite maintenance of mammary eIF2Be and eIF2α abundances during Leu and Lys deficiencies, Milk Protein Yield declined, suggesting that other factors are responsible for mediating effects of Lys and Leu. A deficiency of all 3 BCAA may impair Milk Protein Yield through deactivation of mTORC1-mediated upregulation of eIF2Be and eIF2α abundances.

  • essential amino acid infusions stimulate mammary expression of eukaryotic initiation factor 2be but Milk Protein Yield is not increased during an imbalance
    Journal of Dairy Science, 2015
    Co-Authors: John Doelman, R.v. Curtis, Michelle Carson, J.j.m. Kim, J.a. Metcalf, J P Cant
    Abstract:

    Abstract Essential amino acid (EAA) deficiencies and imbalances were created in lactating cows by using an infusion subtraction protocol to explore effects on Milk Protein Yield and activity state of regulators of mRNA translation in the mammary glands. Six lactating cows on a diet of 11.2% Protein were infused abomasally for 5 d with saline, 563 g/d of a complete EAA mix, or EAA without His, Met, Phe, or Trp in a 6 × 6 Latin square design. Infusion of complete and imbalanced EAA solutions increased mammalian target of rapamycin (mTOR) signaling in the mammary glands, as evidenced by higher ribosomal S6 kinase 1 (S6K1) phosphorylation compared with saline infusion. Total S6K1 abundance was decreased by imbalanced AA infusions. Except for the mixture lacking Phe, infusion of EAA, whether imbalanced or not, increased abundance of total eukaryotic initiation factor 2Be (eIF2Be). A correlation of 0.33 between phosphorylation state of S6K1 and total eIF2Be abundance suggests that an mTOR-mediated upregulation of eIF2Be translation occurred. Despite increased mTOR/eIF2Be signaling, Milk Protein Yields increased only with the complete EAA mixture compared with saline. Low plasma concentrations of His, Met, and Phe during their respective imbalances likely interfered with Protein synthesis. Total abundance and phosphorylation state of eukaryotic initiation factor 2α were not responsible for the interference. Further study of eIF2Be as a regulator of Milk Protein Yield is warranted.

  • Essential amino acid infusions stimulate mammary expression of eukaryotic initiation factor 2Bε but Milk Protein Yield is not increased during an imbalance
    Journal of dairy science, 2015
    Co-Authors: John Doelman, R.v. Curtis, Michelle Carson, J.j.m. Kim, J.a. Metcalf, J P Cant
    Abstract:

    Abstract Essential amino acid (EAA) deficiencies and imbalances were created in lactating cows by using an infusion subtraction protocol to explore effects on Milk Protein Yield and activity state of regulators of mRNA translation in the mammary glands. Six lactating cows on a diet of 11.2% Protein were infused abomasally for 5 d with saline, 563 g/d of a complete EAA mix, or EAA without His, Met, Phe, or Trp in a 6 × 6 Latin square design. Infusion of complete and imbalanced EAA solutions increased mammalian target of rapamycin (mTOR) signaling in the mammary glands, as evidenced by higher ribosomal S6 kinase 1 (S6K1) phosphorylation compared with saline infusion. Total S6K1 abundance was decreased by imbalanced AA infusions. Except for the mixture lacking Phe, infusion of EAA, whether imbalanced or not, increased abundance of total eukaryotic initiation factor 2Be (eIF2Be). A correlation of 0.33 between phosphorylation state of S6K1 and total eIF2Be abundance suggests that an mTOR-mediated upregulation of eIF2Be translation occurred. Despite increased mTOR/eIF2Be signaling, Milk Protein Yields increased only with the complete EAA mixture compared with saline. Low plasma concentrations of His, Met, and Phe during their respective imbalances likely interfered with Protein synthesis. Total abundance and phosphorylation state of eukaryotic initiation factor 2α were not responsible for the interference. Further study of eIF2Be as a regulator of Milk Protein Yield is warranted.