Elevated liver fat content occurs in high-yielding dairy cows during the transition from pregnancy to lactation after fat mobilization and may affect hepatic glucose metabolism, but the degree of liver fat storage is highly variable. Therefore, we studied metabolic and endocrine changes and hepatic glucose metabolism in cows that markedly differ in liver fat content. Multiparous cows from the same herd with high (HFL; n = 10) and low (LFL; n = 10) liver fat contents (mean of d 1, 10, and 21 after calving for each cow, respectively) were studied from 60 d before expected calving to 56 d in milk. Cows were fed ad libitum and all cows received the same diets. Liver samples were taken on d 1, 10, and 21 after calving; mean fat content (+/-SEM) in liver of HFL cows was 174 +/- 9.6 mg/g, whereas mean liver fat content in LFL cows was 77 +/- 3.3 mg/g. Blood samples were taken 20 and 7 d before expected calving and 0, 7, 14, 28, and 56 d after calving to measure plasma concentrations of nonesterified fatty acids, beta-hydroxybutyrate, glucose, insulin, glucagon, insulin-like growth factor-I, and leptin. In liver, glycogen content as well as mRNA levels of phosphoenolpyruvate carboxykinase, pyruvate carboxylase, glucose-6-phosphatase, and glucose transporter were measured by quantitative real-time PCR. Back fat thickness decreased and dry matter intake increased with onset of lactation, and back fat thickness was higher but dry matter intake was lower in HFL than in LFL. Energy-corrected milk yield did not differ between groups, but milk fat content was higher and lactose content was lower in HFL than LFL at the beginning of lactation. Energy balance was more negative in HFL than in LFL. Plasma nonesterified fatty acids and beta-hydroxybutyrate concentrations increased and plasma glucose concentration tended to decrease more in HFL than LFL with onset of lactation. Glucagon to insulin ratios increased more in HFL than LFL with onset of lactation. Hepatic glycogen content was higher in LFL than HFL, whereas mRNA levels of glucose-6-phosphatase and pyruvate carboxylase were higher in HFL than in LFL, and cytosolic phosphoenolpyruvate carboxykinase mRNA level increased similarly after parturition in both groups. In conclusion, an elevated liver fat content was related to greater fat mobilization and reduced feed intake and was associated with effects on hepatic glucose metabolism. As environment and feeding management were the same, individual cow factors were responsible for differences in energy metabolism during the transition period.

Feeding management of the postnatal and preweaning calf has an important impact on calf growth and development during this critical period and affects the health and well-being of the calves. After birth, an immediate and sufficient colostrum supply is a prerequisite for successful calf rearing. Colostrum provides high amounts of nutrient as well as non-nutrient factors that promote the immune system and intestinal maturation of the calf. The maturation and function of the neonatal intestine enable the calf to digest and absorb the nutrients provided by colostrum and milk. Therefore, colostrum intake supports the start of anabolic processes in several tissues, stimulating postnatal body growth and organ development. After the colostrum feeding period, an intensive milk feeding protocol, that is, at least 20% of BW milk intake/day, is required to realise the calf potential for growth and organ development during the preweaning period. Insufficient milk intake delays postnatal growth and may have detrimental effects on organ development, for example, the intestine and the mammary gland. The somatotropic axis as the main postnatal endocrine regulatory system for body growth is stimulated by the intake of high amounts of colostrum and milk and indicates the promotion of anabolic metabolism in calves. The development of the forestomach is an important issue during the preweaning period in calves, and forestomach maturation is best achieved by solid feed intake. Unfortunately, intensive milk-feeding programmes compromise solid feed intake during the first weeks of life. In the more natural situation for beef calves, when milk and solid feed intake occurs at the same time, calves benefit from the high milk intake as evidenced by enhanced body growth and organ maturation without impaired forestomach development during weaning. To realise an intensive milk-feeding programme, it is recommended that the weaning process should not start too early and that solid feed intake should be at a high extent despite intensive milk feeding. A feeding concept based on intensive milk feeding prevents hunger and abnormal behaviour of the calves and fits the principles of animal welfare during preweaning calf rearing. Studies on milk performance in dairy cows indicate that feeding management during early calf rearing influences lifetime performance. Therefore, an intensive milk-feeding programme affects immediate as well as long-term performance, probably by programming metabolic pathways during the preweaning period.

In neonatal calves, nutrient intake shifts from continuous glucose supply via the placenta to discontinuous colostrum and milk intake with lactose and fat as main energy sources. Calves are often born hypoglycemic and have to establish endogenous glucose production (eGP) and gluconeogenesis, because lactose intake by colostrum and milk does not meet glucose demands. Besides establishing a passive immunity, colostrum intake stimulates maturation and function of the neonatal gastrointestinal tract (GIT). Nutrients and nonnutritive factors, such as hormones and growth factors, which are present in high amounts in colostrum of first milking after parturition, affect intestinal growth and function and enhance the absorptive capacity of the GIT. Likely as a consequence of that, colostrum feeding improves the glucose status in neonatal calves by increasing glucose absorption, which results in elevated postprandial plasma glucose concentrations. Hepatic glycogen concentrations rise much greater when colostrum instead of a milk-based colostrum replacer (formula with same nutrient composition as colostrum but almost no biologically active substances, such as hormones and growth factors) is fed. In contrast, first-pass glucose uptake in the splanchnic tissue tended to be greater in calves fed formula. The greater plasma glucose rise and improved energy status in neonatal calves after colostrum intake lead to greater insulin secretion and accelerated stimulation of anabolic processes indicated by enhanced maturation of the postnatal somatotropic axis in neonatal calves. Hormones involved in stimulation of eGP, such as glucagon and cortisol, depend on neonatal diet, but their effects on eGP stimulation seem to be impaired. Although colostrum feeding affects systemic insulin, IGF-I, and leptin concentrations, evidence for systemic action of colostral insulin, IGF-I, and leptin in neonatal calves is weak. Studies so far indicate no absorption of insulin, IGF-I, and leptin from colostrum in neonatal calves, unlike in rodents where systemic effects of colostral leptin are demonstrated. Therefore, glucose availability in neonatal calves is promoted by perinatal maturation of eGP and colostrum intake. There may be long-lasting effects of an improved colostrum supply and glucose status on postnatal growth and development, and colostrum supply may contribute to neonatal programming of performance (milk and growth) in later life, but data proving this concept are missing. Copyright © 2013. American Society of Animal Science .

The pre-weaning period is critical for calf health and growth, and intensive milk feeding programs may assist postnatal development by improving body growth and organ maturation. The aim of the present work was to study the effects of ad libitum milk replacer (MR) feeding on the growth, metabolic adaptation, health, and immune status of newborn calves. Twenty-eight newborn Holstein and Holstein x Charolais crossbred calves were fed ad libitum (ADLIB) or in restricted amounts (6 liters per day; RES) during the first five weeks of life. The MR intake in the ADLIB treatment was gradually reduced at weeks 6 and 7, and all calves then received 6 liters of MR per day until day 60. Blood samples were collected to measure the plasma concentrations of metabolites, insulin, insulin-like growth factor (IGF)-I and IGF binding proteins (IGFBP), immunoglobulins, and acute phase proteins. The expression of mRNA associated with both the somatotropic axis and gluconeogenic enzymes was measured in the liver on day 60. Intensive feeding improved MR intake and growth in ADLIB without influencing concentrate intake. Carcass weight, perirenal fat, and muscle mass were greater in ADLIB. Plasma concentrations of glucose, triglycerides, insulin, and IGF-I were greater, whereas plasma concentrations of β-hydroxybutyrate, total protein, albumin, urea, IGFBP-2 and -4, and fibrinogen were lower at distinct time points in ADLIB. The hepatic mRNA expression of cytosolic phosphoenolpyruvate carboxykinase was greater in ADLIB. Most metabolic and endocrine differences occurred during the MR feeding period, but a slightly greater concentrate intake was associated with increased plasma IGF-I and insulin at the end of the study. The immune and health status of the calves were not affected by MR feeding. However, increased plasma fibrinogen in the RES group suggested differences in the acute phase response.

Background: Systems biology enables the identification of gene networks that modulate complex traits. Comprehensive metabolomic analyses provide innovative phenotypes that are intermediate between the initiator of genetic variability, the genome, and raw phenotypes that are influenced by a large number of environmental effects. The present study combines two concepts, systems biology and metabolic analyses, in an approach without prior functional hypothesis in order to dissect genes and molecular pathways that modulate differential growth at the onset of puberty in male cattle. Furthermore, this integrative strategy was applied to specifically explore distinctive gene interactions of non-SMC condensin I complex, subunit G (NCAPG) and myostatin (GDF8), known modulators of pre- and postnatal growth that are only partially understood for their molecular pathways affecting differential body weight. Results: Our study successfully established gene networks and interacting partners affecting growth at the onset of puberty in cattle. We demonstrated the biological relevance of the created networks by comparison to randomly created networks. Our data showed that GnRH (Gonadotropin-releasing hormone) signaling is associated with divergent growth at the onset of puberty and revealed two highly connected hubs, BTC and DGKH, within the network. Both genes are known to directly interact with the GnRH signaling pathway. Furthermore, a gene interaction network for NCAPG containing 14 densely connected genes revealed novel information concerning the functional role of NCAPG in divergent growth. Conclusions: Merging both concepts, systems biology and metabolomic analyses, successfully yielded new insights into gene networks and interacting partners affecting growth at the onset of puberty in cattle. Genetic modulation in GnRH signaling was identified as key modifier of differential cattle growth at the onset of puberty. In addition, the benefit of our innovative concept without prior functional hypothesis was demonstrated by data suggesting that NCAPG might contribute to vascular smooth muscle contraction by indirect effects on the NO pathway via modulation of arginine metabolism. Our study shows for the first time in cattle that integration of genetic, physiological and metabolomics data in a systems biology approach will enable (or contribute to) an improved understanding of metabolic and gene networks and genotype-phenotype relationships.