Short-term lactation and mammary metabolism responses in lactating goats to graded removal of methionine from an intravenously infused complete amino acid mixture

To investigate the possible pathways of Met deficiency to depress milk protein synthesis, 4 lactating goats fitted with jugular vein, mammary vein, and carotid artery catheters and transonic blood flow detectors on the external pudic artery were used in a 4 x 4 Latin square experiment. Goats were fasted for 24 h followed by a 9-h intravenous infusion of an AA mixture plus glucose. Milk yield was recorded and samples were taken in h 2 to 8 of the infusion period, and mammary biopsy was performed in the last hour. Treatments were graded removal of Met from the infused AA mixture to achieve Met content in the infusate of 100 (complete), 60, 30, or 0% of that in casein. Graded Met removal decreased yield of milk, milk protein, and lactose linearly and tended to decrease yield of milk fat linearly. Milk protein yield decreased to 82, 78, and 69% that of complete mixture infusion, respectively, when the 60, 30, and 0% Met infusate was infused. Circulating Met decreased linearly with graded Met removal. Arterial and venous Met decreased to 36 and 23% that of complete mixture infusion, respectively, when all Met was removed out of the mixture. Concomitant with the decreased circulating concentration was a similar increase in mammary Met affinity as reflected by the linearly increased mammary Met clearance rate. The increased affinity plus the linearly increased mammary blood flow totally offset the negative effect of decreased circulating Met concentration on mammary Met uptake. The overall result was similar mammary Met uptakes across treatments ranging from 285.9 to 339.5 mu mol/h. Mammary uptakes of the other AA measured were generally not affected by treatments except for a linearly decreased Thr uptake and a trend of linearly increased Glu uptake. Consistent with the behavior of an AA mainly catabolized in the liver and mainly used for protein synthesis in peripheral tissues, mammary uptake to milk output ratios of Met measured in the present study ranged from 1.25 to 1.49 and was not affected by treatments. For the other AA measured, the ratio of Thr was linearly decreased and that of Glu was linearly increased by graded Met removal. Graded Met removal linearly elevated circulating urea N and glucose concentrations, indicating enhanced whole-body catabolism of AA and hepatic gluconeogenesis. Treatments had no significant effects on circulating insulin, growth hormone, and the other hormones and metabolites measured. Phosphorylation status of eIF4E binding protein 1 tended to decrease linearly and that of p70S6k was linearly decreased by graded Met removal, indicating depressed signal in the intracellular mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway. In conclusion, results of the present study indicated that the mTORC1 pathway and whole-body AA catabolism rather than mammary uptake appeared the drivers for changes in milk protein synthesis in response to varying Met supply.