Production of protein by the lactating mammary gland is stimulated by intake of dietary energy and protein. Mass-action effects of essential amino acids (EAA) cannot explain all of the nutritional response. Protein synthesis in tissues of growing animals is regulated by nutrients through the mammalian target of rapamycin (mTOR) and integrated stress response (ISR) networks. To explore if nutrients signal through the mTOR and ISR networks in the mammary gland in vivo, lactating cows were feed-deprived for 22 h and then infused i.v. for 9 h with EAA+ glucose (Glc), Glc only, l-Met+l-Lys, l-His, or l-Leu. Milk protein yield was increased 33 and 27% by EAA+Glc and Glc infusions, respectively. Infusions of Met+Lys and His generated 35 and 41%, respectively, of the EAA+Glc response. Infusion of EAA+Glc reduced phosphorylation of the ISR target, eukaryotic initiation factor(eIF) 2, in mammary tissue and increased phosphorylation of the mTOR targets, ribosomal S6 kinase 1 (S6K1) and S6. Both responses are stimulatory to protein synthesis. Glucose did not significantly increase mammary S6K1 phosphorylation but reduced eIF2 phosphorylation by 62%, which implicates the ISR network in the stimulation of milk protein yield. In contrast, the EAA infusions increased (P < 0.05) or tended to increase (P < 0.1) mammary mTOR activity and only His, like Glc, decreased eIF2 phosphorylation by 62%. Despite activation of these protein synthesis signals to between 83 and 127% of the EAA+Glc response, EAA infusions produced less than one-half of the milk protein yield response generated by EAA+Glc, indicating that ISR and mTOR networks exert only a portion of the control over protein yield.
Concentrations of glucose in the external iliac artery feeding one udder half of 14 midlactation Holstein cows were increased by infusion to test the following three hypotheses of mammary function: 1) that mammary glands control their blood supply to maintain intracellular energy balance, 2) that milk precursors are taken out of capillary blood according to mass action kinetics, and 3) that the rate of milk component synthesis is dependent on its precursor's uptake from blood. The first seven cows received 20 g/h glucose during 10 h of infusion. Arterial concentrations of glucose were locally increased by only 10%, and the iliac plasma flow was not affected by glucose infusion, so the next seven cows were given 90 g/h glucose. Quantitative predictions resulting from the hypotheses were that arterial plasma flow would decrease by 32% with 90 g/h glucose infusion, glucose uptakes would increase and acetate, fatty acid, and amino acid uptakes decrease, and milk protein and fat yields and percentages would decrease. Iliac plasma flow decreased 16%, half of what was predicted, which suggests that other regulatory processes besides blood flow control took part in the response. Acetate and fatty acid uptakes by the mammary glands were reduced as predicted because of the lower blood flow, but an unexpected depression in extraction of plasma triacylglycerol also contributed to the reduced fatty acid uptake. Milk fat and protein yields were not affected by the exogenous glucose, falsifying the third hypothesis that milk component secretion is a function of uptake of its precursor. Milk fat and protein percentages declined with glucose infusion because of increased lactose synthesis and secretion of water into milk.
Summary Scintigraphy was used to evaluate digital circulation at 24 h intervals in 11 control horses and in nine horses affected with acute laminitis created by administration of a high‐starch ration. Following intra‐arterial injection of technetium‐99m macroaggregated albumin into the brachiocephalic trunk, static images were acquired of the right front foot. Dynamic radionuclide angiograms and static blood pool images were also obtained after jugular vein injection of technetium‐99m diethylenetriamine pentaacetic acid. These procedures were performed on standing horses, using either minimal or no tranquillisation. Images were analysed quantitatively for parameters indicative of circulation to the whole foot and to specific regions within the foot. There was no evidence of reduced total blood flow to the lamellae during either the developmental or acute phases of laminitis. Total flow tended to increase throughout the peripheral/external regions of the foot, but statistically significant elevations were consistently present only within the lamellae. The increased total blood flow to the lamellae may have been due to elevated capillary flow and/or elevated arteriovenous shunt flow. This study did not support lamellar ischaemia as the primary cause of acute equine laminitis.
To evaluate a close mammary infusion technique for the study of milk protein responses to blood amino acid profile, five early-lactation, multiparous Holstein cows were surgically fitted with catheters in both external iliac arteries. Animals were infused into one arterial catheter with five different solutions on 5 consecutive days in a Latin square design. Infusions began at 0800 h and continued until 1800 h. The five infusates were a 3% saline control, 15 g/h of complete amino acid mix, 15 g/h of imbalanced amino acid mix (minus His), 30 g/h of complete amino acid mix, and 30 g/h of imbalanced amino acid mix (minus His). Cows were fed a total mixed ration twice daily containing 16% crude protein and 1.7 Mcal/kg of net energy for lactation. Infusion of the complete amino acid mix elevated amino acid concentrations in arterial plasma two- to threefold but caused only a small dose-dependent increase in milk protein content and yield. Fat percentage in milk was decreased from 4.08 to 3.35% by the complete amino acid infusions so that the protein:fat ratio climbed from 0.76 on the control to 0.99 with 30 g/h of amino acid. Removal of His from the infusate caused plasma His concentrations to drop but had no effect on any other circulating amino acids. Milk composition was restored to control levels by removal of the single amino acid. A short-term circulating amino acid imbalance depresses milk protein percentage and increases milk fat content in dairy cows.
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