Physiological imbalance (PI) is a situation in which physiological parameters deviate from the normal, and cows consequently have an increased risk of developing production diseases and reduced production or reproduction. Our objectives were to (1) determine the effect of stage of lactation and milk yield on metabolic and production responses of cows during a nutrient restriction period to experimentally increase PI; (2) identify major metabolites that relate to degree of PI; and (3) identify potential biomarkers in milk for on-farm detection of PI throughout lactation. Forty-seven Holstein cows in early [n=14; 49±22 d in milk (DIM); parity=1.6±0.5], mid (n=15; 159±39 DIM; parity=1.5±0.5), and late (n=18; 273±3 DIM; parity=1.3±0.5) lactation were used. Prior to restriction, all cows were fed the same total mixed ration ad libitum. All cows were then nutrient restricted for 4 d by supplementing the ration with 60% wheat straw to induce PI. After restriction, cows returned to full feed. Daily milk yield was recorded and composite milk samples were analyzed for fat, protein, lactose, citrate, somatic cells, uric acid, alkaline phosphatase, β-hydroxybutyrate (BHBA), and milk urea nitrogen. Blood was collected daily and analyzed for metabolites: nonesterified fatty acids (NEFA), BHBA, glucose, plasma urea nitrogen, and insulin. The revised quantitative insulin sensitivity check index (RQUICKI) was calculated for each cow. Liver biopsies collected before and during restriction were analyzed for triglycerides, glycogen, phospholipids, glucose, and total lipid content. A generalized linear mixed model was used to determine the effect of stage of lactation on responses during restriction. Regression analyses were used to examine the effect of pre-restriction levels on changes during restriction. Similar decreases in milk yield among groups indicate that the capacity of individual responses is dependent on milk yield but the coping strategies used are dependent on stage of lactation. Milk yield was a better predictor of feed intake than DIM. Plasma glucose decreased for all cows, and cows in early lactation had increased plasma BHBA, whereas cows in later lactation had increased NEFA during restriction. Milk citrate had the greatest increase (58%) during restriction for all cows. Results reported here identified metabolites (i.e., glucose, NEFA, BHBA, cholesterol) as predictors of PI and identified milk citrate as a promising biomarker for PI on farm.

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Colostrum formation and lactogenesis in the mammary gland and the timing of parturition are regulated by endocrine signals. Changes in progesterone (P4) and prolactin (PRL) are considered key events that inhibit colostrum formation, trigger parturition, and signal the onset of lactation. The goal of our study was to determine if colostrum yield and composition and immunoglobulin transfer are affected by prepartum milking relative to the decrease in P4, peak of PRL, or occurrence of parturition. Twenty-three multiparous cows were randomly assigned to 1 of 2 groups: (1) control with first milking at 4 h postcalving (CON, n = 11), and (2) treatment group with first milking approximately 1 d before calving and second milking at 4 h after parturition (APM, n = 12). Colostrum yields were recorded and proportional samples were analyzed for immunoglobulin G (IgG) concentration. Blood plasma samples for the analyses of P4 and PRL were collected 3 times daily at 8-h intervals for 4 d prepartum and again taken at 4 h after parturition. Total colostrum mass of APM cows was higher than that of CON cows. Immunoglobulin G concentration and protein content did not differ between antepartum milking in APM cows and postpartum milking in CON cows. Colostrum IgG concentration and protein content in APM cows at the postpartum milking were lower compared with the IgG concentration established at the prepartum (APM) and postpartum milkings of CON cows. Immunoglobulin G mass did not differ in first and second colostrum collection in APM cows but was lower compared with that of CON cows. The sum of IgG mass in APM cows (prepartum + postpartum collections) did not differ from that of CON cows. Lactose and fat in milk (concentration and mass) increased from first to second milking in APM cows. Total mass of lactose and fat in APM cows (prepartum + postpartum collections) was greater compared with that of CON cows. The finding that the time of milking relative to parturition, P4 decrease, and PRL peak slightly affected yield and quality of colostrum emphasizes the complex interactions of numerous endocrine and morphological changes occurring during colostrogenesis and lactogenesis in dairy cows. The considerably rapid transfer of immunoglobulins into colostrum of prepartum-milked cows within a few hours leads to the hypothesis that the transfer of IgG can be very fast and-contrary to earlier findings-persist at least until parturition.

Our objective was to investigate the quantitative and qualitative effects of propylene glycol (PG) allocation on postpartum adipose tissue mobilization in overconditioned Holstein cows. Nine ruminally cannulated and arterially catheterized cows were, at parturition, randomly assigned to a ruminal pulse dose of either 500 g of tap water (n = 4) or 500 g of PG (n = 5) once a day. The PG was given with the morning feeding for 4 wk postpartum (treatment period), followed by a 4-wk follow-up period. All cows were fed the same prepartum and postpartum diets. At -16 (±3), 4 (±0), 15 (±1) and 29 (±2) days in milk (DIM), body composition was determined using the deuterium oxide dilution technique, liver and subcutaneous adipose tissue biopsies were collected, and mammary gland nutrient uptake was measured. Weekly blood samples were obtained during the experiment and daily blood samples were taken from -7 to 7 DIM. Postpartum feed intake and milk yield was not affected by PG allocation. The body content of lipid was not affected by treatment, but tended to decrease from 4 to 29 DIM with both treatments. Except for the first week postpartum, no difference in plasma nonesterified fatty acids concentration was noted between treatments in the treatment period. Yet, PG allocation resulted in decreased plasma concentrations of β-hydroxybutyrate (BHB) and increased plasma concentrations of glucose. In the follow-up period, plasma concentrations of nonesterified fatty acids, glucose, and BHB did not differ between treatments. Additionally, the change in abundance of proteins in adipose tissue biopsies from prepartum to 4 DIM was not affected by treatment. In conclusion, the different variables to assess body fat mobilization were concur-rent and showed that a 4-wk postpartum PG allocation had limited effect on adipose tissue mobilization. The main effect was an enhanced glucogenic status with PG. No carry-over effect of PG allocation was recorded for production or plasma metabolites, and, hence, a new period of metabolic adaption to lactation seemed to occur with PG treatment after ceasing PG allocation. Thus, PG seemed to induce a 2-step adaption to lactation, reducing the immediate postpartum nadir and peak of plasma concentration of glucose and BHB, respectively; which is beneficial for postpartum cows at high risk of lipid-related metabolic diseases.

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