During the transition period, dairy cows undergo large metabolic adaptations in glucose, fatty acid, and mineral metabolism to support lactation and avoid metabolic dysfunction. The practical goal of nutritional management during this timeframe is to support these metabolic adaptations. The National Research Council addressed nutritional management of transition cows for the first time in 2001; however, a substantial amount of research has been reported since this publication was released. Results support 2-group nutritional strategies for dry cows to minimize overfeeding of nutrients during the early dry period but increase nutrient supply to facilitate metabolic adaptation to lactation during the late dry period. Increasing the amount of energy supplied through dietary carbohydrate during the prepartum period results in generally positive effects on metabolism and performance of transition cows. Recent research, however, suggests that the form of that carbohydrate (i.e., starch vs. highly digestible neutral detergent fiber) may be of lesser importance. Attempts to increase energy supply by feeding dietary fat sources or decrease energy expenditure by supplying specific fatty acids such as trans-10, cis-12 conjugated linoleic acid to decrease milk fat output during early lactation do not decrease the release of nonesterified fatty acids (NEFA) from adipose tissue. Although the view that nutritional means have limited ability to enhance hepatic export of NEFA as triglycerides in lipoproteins in ruminants has become dogma, recent evidence suggests that nutrients such as choline or specific fatty acids may enhance this process in transi

Four multiparous lactating cows (175 to 220 d in milk [DIM]) were used in a 4 x 4 Latin square design to assess the effects of four doses (0.0, 0.5, 1.0, and 1.5 microg/kg of body weight) of lipopolysaccharide (LPS; Escherichia coli 0111:B4) on performance and plasma metabolite and hormone concentrations. In addition, effects of immune activation on in vitro hepatic metabolic capacity were evaluated in 12 multiparous lactating cows (150 to 220 DIM) infused with 0 (n = 6), 1.0 (n = 4) or 2.0 (n = 2) microg of LPS/kg. Milk production and DMI decreased linearly with LPS dose for 24 h after LPS infusion. Overall mean plasma tumor necrosis factor-alpha, insulin, glucagon, and cortisol concentrations increased linearly with LPS dose, and plasma beta-hydroxybutyrate decreased linearly by dose after LPS infusion. Infusion of LPS decreased the insulin:glucagon molar ratio, but did not affect plasma concentrations of growth hormone, insulin-like growth factor-1, leptin, or L-(+)-lactate. Plasma concentrations of glucose tended to increase initially and subsequently decrease, and there was a quadratic tendency for increased plasma nonesterified fatty acid concentrations after LPS administration. In vitro hepatic capacity for conversion of [1-(14)C]L-(+)-lactate and [1-(14)C]palmitate, but not [1-(14)C]propionate or [1-(14)C]L-alanine, to CO2 increased after LPS administration. Hepatic capacity to convert [1-(14)C]propionate to glucose tended to increase, but neither esterification nor the conversion of palmitate to acid soluble products was altered by LPS. The LPS infusion resulted in significant changes of endocrine mediators responsible for regulation of energy metabolism of lactating cows and tended to alter subsequent in vitro hepatic metabolic capacity.

Multiparous cows (n=34, 89 d in milk, 537 kg) housed in environmental chambers were fed a control total mixed ration or one containing monensin (450 mg/cow per day) during 2 experimental periods (P): (1) thermal neutral (TN) conditions (constant 20°C) with ad libitum intake for 9 d, and (2) heat stress (HS, n=16) or pair-fed [PF; in TN (PFTN); n=18] for 9 d. Heat-stress was cyclical with temperatures ranging from 29.4 to 38.9°C. Rectal temperatures and respiration rates increased in HS compared with PFTN cows (38.4 to 40.4°C, 40 to 93 breaths/min). Heat stress reduced dry matter intake (DMI, 28%), and by design, PFTN cows had similar intakes. Monensin-fed cows consumed less DMI (1.59 kg/d) independent of environment. Milk yield decreased 29% (9.1 kg) in HS and 15% (4.5 kg) in PFTN cows, indicating that reduced DMI accounted for only 50% of the decreased milk yield during HS. Monensin had no effect on milk yield in either environment. Both HS and PFTN cows entered into calculated negative energy balance (-2.7 Mcal/d), and feeding monensin increased feed efficiency (7%) regardless of environment. The glucose response to an epinephrine (EPI) challenge increased (27%) during P2 for both HS and PFTN cows, whereas the nonesterified fatty acid response to the EPI challenge was larger (56%) during P2 in the PFTN compared with the HS cows. Compared with P1, whole-body glucose rate of appearance (Ra) decreased similarly during P2 in both HS and PFTN cows (646 vs. 514 mmol/h). Although having similar rates of glucose Ra, HS cows synthesized approximately 225 g less milk lactose; therefore, on a milk yield basis, glucose Ra decreased (3.3%) in PFTN but increased (5.6%) in HS cows. Regardless of environment, monensin-fed cows had increased (10%) glucose Ra per unit of DMI. From the results we suggest that the liver remains sensitive but adipose tissue becomes refractory to catabolic signals and that glucose Ra (presumably of hepatic origin) is preferentially utilized for processes other than milk synthesis during HS.

In many mammals, lactation success depends on substantial use of lipid reserves and requires integrated metabolic activities between white adipose tissue (WAT) and liver. Mechanisms responsible for this integration in lactation are poorly understood, but data collected in other conditions of elevated lipid use suggest a role for fibroblast growth factor-21 (FGF21). To address this possibility in the context of lactation, we studied high-yielding dairy cows during the transition from late pregnancy (LP) to early lactation (EL). Plasma FGF21 was nearly undetectable in LP, peaked on the day of parturition, and then stabilized at lower, chronically elevated concentrations during the energy deficit of EL. Plasma FGF21 was similarly increased in the absence of parturition when an energy-deficit state was induced by feed restricting late-lactating dairy cows, implicating energy insufficiency as a cause of chronically elevated FGF21 in EL. Gene expression studies showed that liver was a major source of plasma FGF21 in EL with little or no contribution by WAT, skeletal muscle, and mammary gland. Meaningful expression of the FGF21 coreceptor β-Klotho was restricted to liver and WAT in a survey of 15 tissues that included the mammary gland. Expression of β-Klotho and its subset of interacting FGF receptors was modestly affected by the transition from LP to EL in liver but not in WAT. Overall, these data suggest a model whereby liver-derived FGF21 regulates the use of lipid reserves during lactation via focal actions on liver and WAT.

Twenty Holstein cows in early lactation (7 d in milk) were administered 100 microg of Escherichia coli lipopolysaccharide (LPS) dissolved in 10 mL of sterile 0.9% NaCl saline (treatment; TRT) or 10 mL of sterile saline (control) into both right mammary quarters to test the hypothesis that acute experimental mastitis would have negative impacts on aspects of energy metabolism that might lead to the development of metabolic disorders. A primed continuous intravenous infusion (14-micromol/kg of BW priming dose; 11.5-micromol/kg of BW per h continuous infusion) of 6,6-dideuterated glucose was used to determine pre- and posttreatment glucose kinetics using steady-state tracer methodologies. The LPS-treated cows displayed productive, clinical, and physiological signs of moderate to severe inflammation; control cows displayed no signs of immune activation. Pretreatment glucose rates of appearance (Ra) into plasma were similar (715 and 662 +/- 33 mmol/h for TRT and control, respectively) between treatment groups. Intramammary LPS infusion into TRT cows resulted in increased glucose Ra relative to control cows (mean glucose Ra from 150 through 270 min after intramammary infusion were 815 and 674 +/- 21 mmol/h for TRT and control cows, respectively). Furthermore, plasma concentrations of glucose increased, whereas plasma nonesterified fatty acids, glycerol, and beta-hydroxybutyrate concentrations decreased, in TRT relative to control cows. Interestingly, plasma insulin concentration increased dramatically in TRT cows and occurred prior to the small increase in plasma glucose concentration. Although these results only represent the early stages of inflammation, they are not consistent with a causal relationship between mastitis and energy-related metabolic disorders and instead suggest a coordinated protective effect by the immune system on metabolism during the early stages of mammary insult.

Holstein cows (n = 72) entering second or later lactation were used to determine whether productive performance and dry matter intake (DMI) are affected by carbohydrate source in the prepartum diet and chromium-L-methionine (Cr-Met) supplementation throughout the periparturient period. Cows were fed either a TMR with the concentrate portion based on starch-based cereals [high nonfiber carbohydrate (NFC); 1.59 Mcal/kg of net energy for lactation (NEL), 14.4% crude protein (CP), 40.3% NFC] or a TMR with the concentrate portion based on nonforage fiber sources (low NFC; 1.54 Mcal/kg NEL, 14.5% CP, 33.6% NFC) from 21 d before expected parturition until parturition. After parturition all cows were fed a lactation TMR (1.74 Mcal/kg NEL, 16.5% CP, 40.0% NFC). The Cr-Met was supplemented once daily via gelatin capsule at dosages of 0, 0.03, or 0.06 mg of Cr/kg of metabolic body weight. Thus, treatments were in a 2 (carbohydrate source) x 3 (Cr-Met) factorial arrangement. Neither prepartum nor postpartum DMI was affected by prepartum dietary carbohydrate source. Administering increasing amounts of Cr-Met linearly increased milk yield and, subsequently, postpartum DMI. Prepartum carbohydrate source did not affect postpartum milk yield; however, cows fed the low NFC diet tended to yield milk with a lower content of total solids. These data indicate that prepartum carbohydrate source has little influence on performance during the immediate peripartal period, and that increases in milk yield for cows supplemented with Cr-Met are independent of prepartum dietary carbohydrate source.

Thiazolidinediones (TZD) are potent, synthetic ligands for peroxisome proliferator activated receptor-gamma (PPAR-gamma) that reduce plasma nonesterified fatty acids (NEFA) and potentiate the action of insulin in peripheral tissues of several species. Holstein cows (n = 9) entering their second or greater lactation were used to determine whether late prepartum administration of TZD would affect periparturient metabolism and milk production. Cows were limit-fed a total mixed ration (TMR) during the prepartum period to provide no more than 130% of predicted energy requirements. During the postpartum period cows were fed a common TMR for ad libitum intake. Cows were administered either 2,4-TZD (4.0 mg/kg of body weight) or saline (control) by intrajugular infusion once daily from 25 d before expected parturition until parturition. Plasma samples were collected daily from 26 d before expected parturition through 7 d postpartum. Plasma NEFA concentrations decreased during the prepartum period (d -21 to -1; 70 vs. 83 +/- 4 microEq/L) and tended to be decreased during the peripartum period (d -7 to d +7; 113 vs. 205 +/- 32 microEq/L) due to prepartum TZD administration. Plasma concentrations of glucose were not affected by treatment; however, plasma beta-hydroxybutyrate concentrations decreased in TZD-treated cows (8.6 vs. 10.7 +/- 1.7 mg/dL) as parturition approached, and plasma insulin concentrations increased during the peripartum period (0.65 vs. 0.38 +/- 0.07 ng/mL). Postpartum liver triglyceride and glycogen content was not affected by treatment. Prepartum TZD administration tended to increase dry matter intake during the peripartum and postpartum periods (16.6 vs. 14.6 +/- 0.8 kg/d and 20.0 vs. 17.2 +/- 1.2 kg/d, respectively). Milk yield for the first 30 d postpartum and milk composition measured on d 8 postpartum were not affected by treatment. There was no effect of prepartum TZD administration on insulin-dependent glucose utilization assessed using insulin challenge during either the prepartum or postpartum periods. These results suggest that administration of TZD during the late prepartum period has the potential to improve metabolic health and DMI of periparturient dairy cows and warrants further investigation.

Four multiparous lactating cows (175 to 220 d in milk) were used in a 4 x 4 Latin square design to assess the effects of four doses (0.0, 0.5, 1.0, 1.5 microg/kg of body weight) of lipopolysaccharide (LPS; Escherichia coli 0111:B4) on circulating concentrations of macrominerals and vitamin D metabolites. Treatments were dissolved in 100 ml of sterile saline and infused intravenously over a period of 100 min. Blood was sampled immediately before infusion (0 h), at 60-min intervals for 8 h, and at 24 and 48 h postinfusion. Vitamin D metabolites were analyzed in samples collected at 0, 2, 6, 24, and 48 h only. Serum Ca and P concentrations decreased after LPS infusion, but there was no effect on serum magnesium concentration. Plasma 25-OH vitamin D3 and 1,25-(OH)2 vitamin D3 were not affected by LPS infusion; however, when analyzed as 0 vs. all other doses of LPS combined, there was a tendency for plasma 1,25-(OH)2 vitamin D3 concentration to decrease when cows were infused with LPS. The inflammatory response elicited by LPS altered plasma macromineral concentrations, a result that may have important implications for calcium homeostasis and metabolic health of lactating dairy cows.