Effect of hormonal and energy-related factors on plasma adiponectin in transition dairy cows

In transition dairy cows, plasma levels of the insulin-sensitizing hormone adiponectin fall to a nadir at parturition and recover in early lactation. The transition period is also characterized by rapid changes in metabolic and hormonal factors implicated in other species as positive regulators of adiponectin production (i.e., negative energy balance, lipid mobilization) and others as negative regulators (i.e., reduced leptin and insulin and increased growth hormone and plasma fatty acids). To assess the role of onset of negative energy balance and lipid mobilization after parturition, dairy cows were either milked thrice daily (lactating) or never milked (nonlactating) for up to 4 wk after parturition. Plasma adiponectin was 21% higher across time in nonlactating than lactating cows. Moreover, nonlactating cows recovered plasma adiponectin at similar rates as lactating cows even though they failed to lose body condition. Next, we assessed the ability of individual hormones to alter plasma adiponectin in transition dairy cows. In the first experiment, dairy cows received a constant 96-h intravenous infusion of either saline or recombinant human leptin starting on d 8 of lactation. In the second experiment, dairy cows were studied in late pregnancy (LP, starting on prepartum d ?31) and again in early lactation (EL, starting on d 7 postpartum) during a 66-h period of basal sampling followed by 48 h of hyperinsulinemic-euglycemia. In the third experiment, cows were studied either in LP (starting on d ?40 prepartum) or EL (starting on d 7 postpartum) during a 3-h period of basal sampling followed by 5 d of bovine somatotropin treatment. Plasma adiponectin was reduced by an average of 21% in EL relative to LP in these experiments, but neither leptin, insulin, or growth hormone treatment affected adiponectin in LP or EL. Finally, the possibility that plasma fatty acids repress plasma adiponectin was evaluated by intravenous infusion of a lipid emulsion in nonpregnant, nonlactating cows in the absence or presence of glucagon for 16 consecutive hours. The intralipid infusion increased plasma fatty acid concentration from 102 to over 570 µM within 3 h but had no effect on plasma adiponectin irrespective of presence or absence of glucagon. Overall, these data suggest that energy balance around parturition may regulate plasma adiponectin but do not support roles for lipid mobilization or sustained changes in the plasma concentration of leptin, insulin, growth hormone, or fatty acids.     

Effect of chronic growth hormone treatment on responses to epinephrine and thyrotropin-releasing hormone in lactating cows

Bovine growth hormone was administered to four Holstein cows (late lactation) in a Latin square. Treatments were 1) control, subcutaneous injection of placebo, 2) subcutaneous injection of 25 IU growth hormone on alternate days, 3) daily subcutaneous injection of 25 IU growth hormone, and 4) continuous subcutaneous infusion of 25 IU/d growth hormone. Intravenous challenges of epinephrine and thyrotropin-releasing hormone were administered separately on the 1st d after a 12-d interval of growth hormone treatment. Baseline concentrations of nonesterified fatty acids in plasma were not affected by growth hormone treatment. However, release of nonesterified fatty acids to epinephrine challenge was positively related to amount of growth hormone in plasma during treatment and was correlated with milk fat yield and milk energy secretion. Growth hormone release following thyrotropin-releasing hormone was negatively related to amount of growth hormone in plasma during treatment. Release of prolactin to thyrotropin-releasing hormone challenge was not related to average daily dose of exogenous growth hormone. The galactopoeitic action of growth hormone may be partly attributable to its effects on responsiveness of adipose tissue to a lipolytic stimulus but apparently is not associated with changes of pituitary sensitivity to thyrotropin-releasing hormone. Results are consistent with growth hormone functioning as a homeorhetic control of nutrient partitioning.     

Temporal changes in plasma concentrations of hormones and metabolites in pasture-fed dairy cows during extended lactation

This experiment measured variations in plasma concentrations of metabolic hormones and metabolites in cows undergoing extended lactations of up to 670 d at 2 planes of nutrition. Thirty-seven Holstein-Friesian cows that calved in late winter were selected for varying milk yield and then managed for a lactation of 670 d by delaying breeding until approximately 450 d in milk (DIM). Cows grazed fresh pasture supplemented with pasture silage or hay and crushed wheat or triticale grain. Dietary intake was reduced by approximately 1.8 kg (dry matter) grain/cow per day for 19 of the cows from 300 DIM until the end of lactation to assess the effect of restricted energy intake on the persistency of milk production. Samples of blood were collected monthly from each cow to measure plasma concentrations of selected hormones and metabolites. Dietary restriction beyond 300 DIM reduced yields of milk, protein, and fat, but did not alter the proportion of cows reaching the 670-d lactation target. Dietary restriction had no effect on cow BW or plasma concentrations of any hormones or metabolites. Overall, blood plasma concentrations of insulin-like growth factor-I, leptin, and glucose were elevated from 301 to 600 DIM compared with 0 to 300 DIM, whereas concentrations of growth hormone and nonesterified fatty acids were lower after 300 DIM. Plasma concentrations of insulin and prolactin were unaffected by stage of lactation, but prolactin concentrations increased during summer. These changes were consistent with a decrease in milk yield and an increase in the partitioning of nutrients to body tissue gain, primarily adipose tissue, throughout the later stages of the extended lactation. Cows that continued milking beyond 600 DIM had increased plasma concentrations of growth hormone and decreased concentrations of glucose and leptin compared with cows that milked <600 DIM. These differences, coupled with reduced body weight gain, indicated an increased priority for nutrient partitioning to milk production at the expense of body tissue gain throughout the extended lactation period in cows with greater lactation persistency.     

Regulation of messenger ribonucleic acid expression for gluconeogenic enzymes during glucagon infusions into lactating cows.

The effects of glucagon infusions on expression of mRNA for enzymes that regulate gluconeogenesis were studied in lactating cows. Normal cows and cows with fatty liver that were susceptible to ketosis were assigned to either glucagon-treated or control groups. Glucagon at 0 or 10 mg/d was infused for 14 d beginning at d 21 postpartum. In normal cows, glucagon infusions increased concentrations of both plasma glucagon and glucose, which caused plasma insulin to increase. Consequently, hepatic phosphoenolpyruvate carboxykinase mRNA decreased during wk 1 of glucagon infusions. Glucagon infusions into cows with fatty liver also increased plasma glucagon and glucose, but concentrations of plasma insulin and hepatic phosphoenolpyruvate carboxykinase mRNA did not change. More phosphoenolpyruvate carboxykinase mRNA was present in the livers of cows with fatty liver than in livers of normal cows. In a follow-up experiment with midlactation cows, 3.5-h infusions of glucagon at 14 mg/d increased plasma glucose and insulin and decreased plasma nonesterified fatty acids and hepatic glycogen. Hepatic phosphoenolpyruvate carboxykinase mRNA was decreased 41%, pyruvate carboxylase mRNA was increased 50%, but fructose-1,6-bisphosphatase mRNA did not change. We conclude that the expression of the hepatic phosphoenolpyruvate carboxykinase gene in normal cows is inhibited by insulin to balance elevated carbohydrate status during glucagon infusions; however, inhibited expression of hepatic phosphoenolpyruvate carboxykinase mRNA probably is not involved in the pathogenesis of lactation ketosis.     

Duodenal rapeseed oil infusion in early and midlactation cows. 2. Voluntary intake, milk production, and composition

Rapeseed oil was infused continuously (1.0 to 1.1 kg/d) into the proximal duodenum of rumen- and duodenum-fistulated Holstein Friesian multiparous cows from 17 d before to 21 d after calving (6 oil-infused cows vs. 6 controls) (early lactation trial) or after 100 d of lactation (mid-lactation trial, 9 cows in a crossover design). Oil-free DM intake was lower in oil-infused than in control cows in early (wk 3) and midlactation trials. In early lactation, milk production tended to be lower in oil-infused cows but milk composition was unchanged. In the midlactation trial, milk yield and lactose content were unaffected, milk fat content was slightly increased, and protein content sharply decreased in oil-infused cows. Rapeseed oil infusion had a positive effect on the total metabolizable energy absorbed during the wk 1 and 2 of lactation but not in the wk 3 or in the midlactation trial. Calculated energy balance was higher in oil-infused cows in both trials. In early lactation, oil infusion did not reduce losses in empty BW, condition score, subcutaneous adipose cell diameter, and estimated body lipids. In midlactation, empty BW and body condition score were decreased by oil infusion. Results suggested that energy control mechanisms limited DM intake in oil-infused cows, possibly limiting milk yield increase and the availability of precursors for milk protein synthesis. Body reserve mobilization was not reduced but could even have been increased by oil infusion.     

The housekeeping genes GAPDH and cyclophilin are regulated by metabolic state in the liver of dairy cows

Steady-state levels of mRNA are often used to infer treatment effects on the levels of the corresponding protein. In addition, an internal standard RNA is usually measured to document specificity of treatment and to correct for intersample variation. Our objective was to evaluate whether glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and cyclophilin could be used as internal standards when studying changes in hepatic gene expression in dairy cows. Hepatic expression of GAPDH and cyclophilin was measured in 6 cows in late pregnancy (28 d prepartum) and early lactation (10 d postpartum). Each gene displayed 2- to 3-fold higher expression in early lactation than in late pregnancy. Next, we determined whether negative energy balance alone or in combination with exogenous growth hormone could mimic the effects of early lactation. Late-lactating cows were fed 120% of predicted energy requirements or 33% of maintenance requirements. During each feeding period, cows were administered excipient or bovine somatotropin in a single-reversal design with 4-d periods separated by a 2-d interval. Underfeeding increased hepatic expression of GAPDH and cyclophilin by 1- to 2-fold, whereas bovine somatotropin had no effect. Finally, the effects of insulin were studied by performing hyperinsulinemic-euglycemic clamps in late pregnancy (28 d prepartum) and early lactation (28 d postpartum). Hyperinsulinemia reduced GAPDH expression in both states, and cyclophilin expression in early lactation. In conclusion, GAPDH and cyclophilin are regulated in the liver of dairy cows and should not be used to standardize hepatic gene expression in studies involving the transition period, undernutrition, and sustained changes in plasma insulin.     

Analysis of daily body weight of high-producing dairy cows in the first one hundred twenty days of lactation and associations with ovarian inactivity

The objective of this study was to investigate, describe, and quantify daily body weight (BW) changes in the first 120 d of lactation in high-producing dairy cows. Data included 255,287 daily BW measurements from 2,167 Israeli Holstein dairy cows originating from 7 commercial dairy farms. Individual series of measurements were first smoothed using cubic splines for generating variables representing BW changes in early lactation and further analysis of the data. To construct standard BW curves stratified by parity and adjusted for farm, mixed models for repeated measurements were fit to the smoothed data, and least squares means for day in lactation were plotted. Time-series analysis techniques using polynomial functions of day in lactation and pairs of sine and cosine functions representing 7- and 21-d cycles were performed separately on each individual series of measurements. Additionally, generalized estimating equations were used to perform similar analysis on the data set as a whole. Mean days from calving to nadir BW increased significantly from first to later parities, as did mean BW loss from calving to nadir. The first-parity cow lost 6.5% of her BW from calving to d 29 in lactation, and second-parity and greater-parity cows lost 8.5 and 8.4% of their BW to d 34 and 38 in lactation, respectively. After nadir BW was reached, first-parity cows regained relative BW at a greater rate than did older parity cows. The trend in BW was nonlinear. A 7-d cycle was present in 247 cows (11.4%) and a 21-d cycle was present in 715 cows (33.0%). Presence of a 21-d cycle was associated with a 33% reduction in the risk of being diagnosed with inactive ovaries. Fewer days from calving to nadir BW and smaller BW loss from calving to nadir, coupled with a faster post-nadir increase in relative BW in first-parity cows compared with older cows indicated a smaller energy deficit in early lactation. Association between 21-d cycles in BW and ovarian activity suggest that these cycles were physiological and related to the estrous cycle. Therefore, monitoring them could be useful for indirectly assessing ovarian activity in a herd.     

Alleviation of fatty liver in dairy cows with 14-day intravenous infusions of glucagon.

Twenty multiparous cows were fed additional concentrate during the final 30 d prepartum to cause susceptibility to fatty liver. From 14 to 42 d postpartum, all cows were subjected to a protocol to induce fatty liver and ketosis. To test glucagon as a treatment for fatty liver, either glucagon at 10 mg/d or excipient was infused via the jugular vein from 21 to 35 d postpartum. All cows had fatty liver at 14 d postpartum and became ketonemic and hypoglycemic during the induction of ketosis. Glucagon increased plasma glucose to 142% of that of controls throughout the 14-d treatment. The hypoinsulinemia present in cows with fatty liver was not affected by glucagon. Plasma beta-hydroxybutyrate and nonesterified fatty acids were decreased by glucagon. At 6 d postpartum, liver triacylglycerol averaged 12.9% of liver (wet weight basis). Glucagon had decreased triacylglycerol content of livers by 71% at d 35. Glycogen was 1.0% of the wet weight of livers at 6 d in milk, but it was decreased by glucagon to 0.5% at 2 d after glucagon began. Glycogen then increased in cows treated with glucagon until at 38 d in milk liver glycogen was 3.7% versus 1.6% in controls. Our results document that glucagon decreases the degree of fatty liver in early lactation dairy cows, which also decreases the incidence of ketosis after alleviation of fatty liver.     

Dietary trans octadecenoic acids upregulate the liver gene encoding peroxisome proliferator-activated receptor-alpha in transition dairy cows

Effects of feeding calcium salts of conjugated linoleic acid (CLA) or trans octadecenoic acids (trans 18:1) on lipid metabolism and hepatic contents of mRNA encoding carnitine palmitoyltransferase 1 (CPT1), microsomal triglyceride transfer protein (MTP) and peroxisome proliferator-activated receptor alpha (PPARalpha) were examined in 15 early post-partum Holstein cows. Dietary treatments were initiated at approximately 4 weeks prior to expected calving dates and continued for 7 weeks post partum. Treatments prepartum consisted of 1) a basal diet (Control), 2) basal diet+150 g/d of CLA mix (CLA), or 3) basal diet+150 g/d of trans 18:1 mix (TRANS). Intakes of calcium salts of CLA and trans 18:1 mixes were adjusted to 225 g/d during the 7-week postpartum treatment period. Blood samples were collected at weeks 1, 2 and 4 post partum and plasma was harvested immediately for subsequent hormone and metabolite assays. Concentrations of insulin, insulin-like growth factor-I (IGF-I), and leptin in blood did not vary among cows fed the three diets. Plasma nonesterified fatty acid (NEFA) concentrations decreased between weeks 1 and 4 of lactation and were lower in cows fed the diet supplemented with trans 18:1 than in those fed a control diet at week 2 post partum. Periparturient fat supplementation had no detectable effects on CPT1 mRNA content in the liver. Steady-state concentration of MTP mRNA in the liver was greater in the TRANS treatment group than in the control group at week 1 postpartum. Feeding trans 18:1 supplements to transition dairy cows upregulated hepatic PPARalpha mRNA content during the first month of lactation. Under the present experimental conditions, dietary CLA had minimal effects on plasma and hepatic lipid metabolite concentrations in early lactation Holstein cows. Results indicate that dietary trans fatty acids may affect liver lipid metabolism in post-partum dairy cows through alterations in PPARalpha gene expression.     

Physiological effects of whole cottonseed in the diet of lactating dairy cows

With 32 lactating Holstein cows we evaluated physiological effects of gossypol and cyclopropenoid fatty acids in diets containing 18.5% whole cottonseed (dry matter) based on corn, corn silage, and soybean meal. All cows consumed a control diet for the first 2 wk of lactation and then were assigned to either control or whole cottonseed diet for the remainder of their lactation. Milk production, milk fat and protein percentages, and daily dry matter intake were measured. Dry matter intakes were less for cows consuming the whole cottonseed diet, but net energy intake was similar for all diets. Milk fat from cows consuming whole cottonseed contained detectable concentrations of cyclopropene fatty acids. Total lipid in plasma, total serum cholesterol, serum gossypol, and apparent liver gossypol concentrations were greater in cows fed whole cottonseed. Gossypol and cyclopropenoid fatty acids appeared to be absorbed from the gut of cows fed whole cottonseed. Small amounts of gossypol in serum and liver tissue and small amounts of cyclopropene fatty acids in adipose tissue lipids and milk fat indicate a need to elucidate the significance of these physiologically active compounds in the human diet and their biological effects on lactating dairy cows.     

Invited review: pathology, etiology, prevention, and treatment of fatty liver in dairy cows

Fatty liver (i.e., hepatic lipidosis) is a major metabolic disorder of many dairy cows in early lactation and is associated with decreased health status and reproductive performance. In severe cases, milk production and feed intake are decreased. Therefore, a practical preventative or an efficacious treatment of fatty liver could save millions of dollars yearly in treatment, replacement, and production losses for dairy farmers. Fatty liver develops when the hepatic uptake of lipids exceeds the oxidation and secretion of lipids by the liver, which usually is preceded by high concentrations of plasma NEFA mobilized from adipose tissue. Excess lipids are stored as triacylglycerol in the liver and are associated with decreased metabolic functions of the liver. Liver can be categorized into normal liver or mild, moderate, or severe fatty liver; the latter can be subdivided further into nonencephalopathic severe fatty liver and hepatic encephalopathy. Insufficient or unbalanced dietary intake, obesity, and elevated estrogen concentrations are involved in the etiology of fatty liver, which is associated with greater incidence of dystocia, diseases, infections, and inflammations. Because even mild fatty liver is associated with decreased health status and reproductive performance of dairy cows, prevention of fatty liver by supplying cows with sufficient nutrients and a clean and health-promoting environment in the peripartal period would reduce production losses of cows more than would any treatment of fatty liver. This, however, might not be enough for cows that are obese or do not eat well, had calving difficulties or twins, have metabolic or infectious diseases, or are in severe negative energy balance because of high milk production immediately after calving. Potential and commonly used preventatives, as well as treatments, are discussed in the review. Currently, detection of fatty liver is possible only by minor surgery. Ultrasonic techniques offer a potential tool to noninvasively detect fatty liver. Future gene-array and proteomic studies may provide means to detect early molecular events in the etiology of fatty liver plus their connection with immune function and reproductive performance so that more effective treatments and preventatives of fatty liver can be developed. Such advances hopefully will make fatty liver a problem of the past.     

Relationship of insulin concentration to blood metabolites in the dairy cow.

Jugular blood samples were taken at regular intervals from 31 ketosis-prone cows from 2 wk prepartum to 7 wk postpartum. Eleven cows exhibited elevated blood ketones and depressed blood glucose indicative of subclinical ketosis. There were no significant differences between means of normal and subclinically-ketotic cows in serum insulin or blood metabolites prior to calving. However, in early lactation, those cows which developed ketosis showed depressed serum insulin, blood glucose, and plasma triglycerides with elevated ketones, acetate in blood, and free fatty acids and cholesterol in plasma. Milk production was also lower in ketotic cows. Correlations within cow between serum insulin and glucose, total ketones, acetate of blood and free fatty acids, triglycerides, and cholesterol in plasma were .014,--.307, .080,--.421, .413, and -.002 for normal cows and .348, -.425, -.324, -.317, .298, and -.131 for subclinically-ketotic cows. It is suggested that low insulin during ketosis is a reflection of depressed blood glucose and, consequently, adipose lipolysis and hepatic ketogenesis are accentuated while acetate utilization and hepatic triglyceride release are depressed.     

Potential treatment of fatty liver with 14-day subcutaneous injections of glucagon

Fatty liver is a major metabolic disease of dairy cows in early lactation that can be treated with 14-d continuous, intravenous infusions of 10 mg/d of glucagon. The objective was to test whether similar effects can be obtained with 14-d subcutaneous 7.5- or 15-mg daily dosages of glucagon beginning at d 8 postpartum. Multiparous Holstein cows (n = 32) were grouped on the basis of their liver triacylglycerol concentration at d 8 postpartum into "normal" (n = 8; triacylglycerol < 1% liver wet wt) and "susceptible" (n = 24; triacylglycerol > 1% liver wet wt) cows. Susceptible cows were assigned randomly to three groups and beginning at d 8 postpartum received 0, 2.5, or 5 mg of glucagon in 60 ml of saline by subcutaneous injections every 8 h for 14 d. Beginning at d 8 postpartum, normal cows received 60 ml of saline by subcutaneous injections every 8 h for 14 d. Both dosages of glucagon increased concentrations of plasma glucose and insulin and decreased concentrations of plasma nonesterfied fatty acids. Glucagon injections of 15 mg/d decreased concentrations of liver triacylglycerol in cows older than 3.5 yr, but not in younger multiparous cows. Our results document that subcutaneous injections of glucagon have the potential to decrease the degree of fatty liver in older dairy cows in early lactation.     

Adaptations of Glucose and Long-Chain Fatty Acid Metabolism in Liver of Dairy Cows during the Periparturient Period

Tremendous metabolic and endocrine adjustments must be made as dairy cows move from late gestation to early lactation. Requirements for glucose and metabolizable energy increase two- to threefold from 21 d before to 21 d after parturition. The liver must adapt quickly to provide the increased glucose needed to support high milk production, and to process the flood of nonesterified fatty acids taken up from extensive mobilization of adipose triglycerides. While the end results of these adaptations are well known, much less is known about the cellular and molecular mechanisms underpinning hepatic adaptation to lactation. Increases in metabolic activity per gram of liver tissue, not just increased liver mass, are responsible for increased metabolism. Compared with activities present at 21 d before parturition, the capacity of liver tissue isolated at 1 d postpartum to convert alanine (an important glucogenic amino acid) to glucose increases more on a percentage basis than does gluconeogenic capacity from propionate. Likewise, hepatic abundance of mRNA for pyruvate carboxylase increases around calving, whereas mRNA for phosphoenolpyruvate carboxykinase does not. These changes in gluconeogenic enzymes suggest that amino acids from body and feed protein may be critically important sources of glucose for peripartal cows. Hepatic tissue from cows 1 d postpartum has greater rates of palmitate esterification, total and peroxisomal beta-oxidation of palmitate, and activity of mitochondrial carnitine palmitoyltransferase than hepatic tissue from the same cows 21 d prepartum. Prepartal nutrition has been shown to modulate some of these metabolic adaptations in the liver. Effects of hormones and cytokines that mediate adaptive responses to environmental and infectious stressors (or the lack of “cow comfort”) have not been investigated. Techniques of modern biochemistry promise to further our understanding of the mechanisms of metabolic adaptation during the peripartal period, and to quantify the effects of nutrition and environment during pre- and postpartum periods on hepatic glucose and lipid metabolism.     

The effect of dry period length and postpartum level of concentrate on milk production,energy balance,and plasma metabolites of dairy cows across the dry period and in early lactation

Shortening or omitting the dry period (DP) improves energy balance (EB) in early lactation because of a reduction in milk yield. Lower milk yield results in lower energy demands and requires less energy intake. The aim of this study was to evaluate the effects of DP length and concentrate level postpartum on milk yield, feed intake, EB, and plasma metabolites between wk ?4 and 7 relative to calving of cows of second parity or higher. Holstein-Friesian dairy cows (n = 123) were assigned randomly to 1 of 2 DP lengths: 0-d DP (n = 81) or 30-d DP (n = 42). Prepartum, cows with a 0-d DP received a lactation ration based on grass silage and corn silage (6.4 MJ of net energy for lactation/kg of dry matter). Cows with a 30-d DP received a dry cow ration based on grass silage, corn silage, and straw (5.4 MJ of net energy for lactation/kg of dry matter). Postpartum, all cows received the same basal lactation ration as provided to lactating cows prepartum. Cows with a 0-d DP were fed a low level of concentrate up to 6.7 kg/d based on the requirement for their expected milk yield (0-d DP-L; n = 40) or the standard level of concentrate up to 8.5 kg/d (0-d DP-S; n = 41), which was equal to the concentrate level for cows with a 30-d DP (30-d DP-S; n = 42) based on requirements for their expected milk yield. Prepartum dry matter intake, concentrate intake, basal ration intake, energy intake, plasma β-hydroxybutyrate (BHB), and insulin concentrations were greater and plasma free fatty acids (FFA) and glucose concentrations were lower, but EB was not different in cows with a 0-d DP compared with cows with a 30-d DP. During wk 1 to 3 postpartum, milk fat yield and plasma BHB concentration were lower and dry matter intake and concentrate intake were greater in cows with a 0-d DP compared with cows with a 30-d DP. During wk 4 to 7 postpartum, fat- and protein-corrected milk (FPCM), lactose content, and lactose and fat yield were lower in 0-d DP-L or 0-d DP-S cows compared with 30-d DP-S cows. Basal ration intake, EB, body weight, plasma glucose, and insulin and insulin-like growth factor-1 concentrations were greater and plasma FFA and BHB concentrations were lower in 0-d DP-L and 0-d DP-S cows compared with 30-d DP-S cows. Concentrate and energy intake were lower in 0-d DP-L cows than in 0-d DP-S or 30-d DP-S cows. Milk yield and concentrations of plasma metabolites did not differ in wk 4 to 7, although EB was lower in wk 6 and 7 postpartum in 0-d DP-L cows than in 0-d DP-S cows. In conclusion, a 0-d DP reduced milk yield and improved EB and metabolic status of cows in early lactation compared with a 30-d DP. Reducing the postpartum level of concentrate of cows with a 0-d DP did not affect fat- and protein-corrected milk yield or plasma FFA and BHB concentrations in early lactation but did reduce EB in wk 6 and 7 postpartum.     

Effects of fat and methionine hydroxy analog on prevention or alleviation of fatty liver induced by feed restriction

Two trials were conducted to examine the effects of supplemental methionine, provided as methionine hydroxy analog 13 g/d), or fat (454 g of calcium salts of long-chain fatty acids/d) on hepatic triglyceride concentration. In the first experiment, methionine hydroxy analog or fat was fed during feed restriction to determine if hepatic triglyceride accumulation is affected. The objective of the second experiment was to determine if feeding fat or methionine hydroxy analog influences the rate of triglyceride depletion from the liver of cows in positive energy balance following the induction of fatty liver by feed restriction. In experiment 1, feeding methionine hydroxy analog decreased plasma glucose, increased plasma nonesterified fatty acids, and had no effect on liver triglyceride. Feeding fat increased plasma nonesterified fatty acids and increased hepatic triglyceride during the 10-d feed restriction period. In experiment 2, feeding fat decreased the rate of triglyceride depletion from liver when cows were allowed to resume ad libitum consumption of feed; methionine hydroxy analog had no effect. Results of these studies indicate that feeding supplemental fat or methionine hydroxy analog at levels tested does not prevent or alleviate fatty liver induced by feed restriction.     

Responses of plasma glucose and nonesterified fatty acids to intravenous insulin tolerance tests in dairy cows during a 670-day lactation

The metabolic response of dairy cows undergoing an extended lactation to an insulin tolerance test (ITT) was investigated. Twelve multiparous Holstein-Friesian cows that calved in late winter in a pasture-based system were managed for a 670-d lactation by delaying rebreeding. Four 5-wk experimental periods commenced at approximately 73, 217, 422, and 520 d in milk (DIM). Cows were offered a diet of perennial ryegrass (73 and 422 DIM) or pasture hay and silage (217 and 520 DIM) supplemented with 1 kg dry matter (DM) of grain (control; CON) or 6 kg DM of grain (GRN). Daily energy intake was approximately 160 and 215 MJ of metabolizable energy/cow for CON and GRN, respectively. At all other times, cows were managed as a single herd and grazed pasture supplemented with grain to an estimated daily intake of 180 MJ of metabolizable energy/cow. Cows were fitted with a jugular catheter during the final week of each experimental period. An ITT using 0.12 IU of insulin/kg of body weight (BW) was conducted on each cow at approximately 100, 250, 460, and 560 DIM. Cows in the GRN treatment had greater milk yield, milk solids yield, and BW than cows in the CON treatment. Within treatment, individual cow responses to the ITT were highly variable. Plasma glucose and nonesterified fatty acid (NEFA) concentrations declined at all stages of lactation. The clearance rate of plasma glucose was slower before 300 DIM than after 300 DIM, which indicates greater inhibition of hepatic glucose synthesis and uptake of glucose by insulin-dependent tissues later in the lactation. The clearance rate, area under the curve, and recovery of plasma NEFA were greatest at 100 DIM, indicating greater responsiveness to the antilipolytic effect of insulin in early lactation, but also greater lipolytic responsiveness. The variation in response to the ITT was mostly a result of DIM rather than diet. However, the plasma NEFA response showed interactions between diet and DIM, indicating that energy intake may affect tissue responses to insulin. The responsiveness of peripheral tissues to insulin, primarily adipose tissue, changed throughout a 670-d lactation and contributed to a greater proportion of nutrients being partitioned to body reserves at the expense of milk yield as lactation progressed. Both stage of lactation and dietary intake have a role in the determination of whole-body and peripheral tissue responses to insulin; however, the exact mechanisms in control of this are unclear.     

Relationships among milk yield,body condition,cow weight,and reproduction in spring-calved Holstein-Friesians

Relationships among milk production, body condition score (BCS), body weight (BW), and reproduction were studied using logistic regression on data from 6433 spring-calving Holstein-Friesian dairy cows in 74 commercial herds. Multivariate models were adjusted for herd, breeding value for milk yield, proportion of Holstein-Friesian genes, lactation number, calving period, and degree of calving assistance. Significant associations between reproductive measures and components of energy balance were identified. Higher 200-d milk protein content and higher protein-to-fat ratio at start of breeding were associated with increased likelihood of submission for breeding in the first 21 d of the breeding season (SR21). High 100-d cumulative milk yield as a proportion of estimated 305-d milk yield (low persistency) was associated with a lower likelihood of pregnancy to first service (PREG1), whereas cows reaching peak milk yields earlier tended to have higher PREG1. Cows that reached nadir milk protein content relatively late in lactation had lower PREG1. Milk yield at first service and 305-d milk protein content were positively associated with the likelihood of pregnancy after 42 d of breeding (PR42). Higher 305-d milk lactose content was associated with increased PREG1 and PR42. Mean BCS at 60 to 100 d of lactation was positively associated with both SR21 and PR42, whereas nadir BCS was positively associated with PREG1. Cows with precalving BCS > 3.0 that also lost > 0.5 BCS unit by first service had lower PR42. More BW gain for 90 d after start of breeding was associated with higher SR21 and PREG1; more BW gain for 90 d after first service was associated with higher PR42. Milk protein and lactose content, BCS, and BW changes are important tools to identify cows at risk of poor reproduction.     

Metabolic effects of abomasal L-carnitine infusion and feed restriction in lactating Holstein cows

l-Carnitine is required for mitochondrial fatty acid oxidation, but the effects of carnitine supplementation on nutrient metabolism during dry matter intake depression have not been determined in dairy cows. Studies in other species have revealed responses to l-carnitine that may be of specific benefit to dairy cows during the periparturient period. Eight lactating Holstein cows (132 ± 36 d in milk) were used in a replicated 4 × 4 Latin square experiment with 14-d periods. Treatments were factorial combinations of abomasal infusion of either water or l-carnitine (20 g/d; d 5 to 14) and either ad libitum or restricted intake (50% of previous 5-d dry matter intake; d 10 to 14) of a balanced lactation diet. Liver and muscle biopsies were obtained on d 14 of each period. Feed restriction induced negative balances of energy and metabolizable protein. In feed-restricted cows, carnitine infusion increased 3.5% fat-corrected milk yield compared with those infused with water. Total carnitine concentration in liver was increased in feed-restricted cows infused with carnitine but not in feed-restricted cows infused with water. Carnitine infusion stimulated in vitro oxidation of [1-¹⁴C] palmitate to acid-soluble products and decreased the proportion of [1-¹⁴C] palmitate that was converted to esterified products by liver slices. Feed-restricted cows infused with carnitine had lower liver total lipid concentration and tended to have decreased triglyceride accumulation compared with feed-restricted cows infused with water. Plasma nonesterified fatty acid concentration was not altered by carnitine infusion but was increased by feed restriction; serum β-hydroxybutyric acid was increased by carnitine infusion in feed-restricted cows. In cows fed for ad libitum intake, carnitine infusion affected β-hydroxybutyric acid, insulin, and urea N in serum, liver glycogen concentration, and in vitro alanine oxidation by liver slices, suggesting that hepatic and peripheral nutrient metabolism was influenced. l-Carnitine infusion effectively decreased liver lipid accumulation during feed restriction as a result of greater capacity for hepatic fatty acid oxidation. Further research examining dietary supplementation of l-carnitine during the periparturient period is warranted.