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During the transition period, the lipid metabolism of dairy cows is markedly affected by energy status. Fatty liver is one of the main health disorders after parturition. The aim of this study was to evaluate the effects of a negative energy balance (NEB) at 2 stages in lactation [NEB at the onset of lactation postpartum (p.p.) and a deliberately induced NEB by feed restriction near 100 d in milk] on liver triglyceride content and parameters of lipid metabolism in plasma and liver based on mRNA abundance of associated genes. Fifty multiparous dairy cows were studied from wk 3 antepartum to approximately wk 17 p.p. in 2 periods. According to their energy balance in period 1 (parturition to wk 12 p.p.), cows were allocated to a control (CON; n = 25) or a restriction group (RES; 70% of energy requirements; n = 25) for 3 wk in mid lactation starting at around 100 d in milk (period 2). Liver triglyceride (TG) content, plasma nonesterified fatty acids (NEFA), and β-hydroxybutyrate were highest in wk 1 p.p. and decreased thereafter. During period 2, feed restriction did not affect liver TG and β-hydroxybutyrate concentration, whereas NEFA concentration was increased in RES cows as compared with CON cows. Hepatic mRNA abundances of tumor necrosis factor α, ATP citrate lyase, mitochondrial glycerol-3-phosphate acyltransferase, and glycerol-3-phosphate dehydrogenase 2 were not altered by lactational and energy status during both experimental periods. The expression of fatty acid synthase was higher in period 2 compared with period 1, but did not differ between RES and CON groups. The mRNA abundance of acetyl-coenzyme Acarboxylase showed a tendency toward higher expression during period 2 compared with period 1. The solute carrier family 27 (fatty acid transporter), member 1 (SLC27A1) was upregulated in wk 1 p.p. and also during feed restriction in RES cows. In conclusion, the present study shows that a NEB has different effects on hepatic lipid metabolism and TG concentration in the liver of dairy cows at early and later lactation. Therefore, the homeorhetic adaptations during the periparturient period trigger excessive responses in metabolism, whereas during the homeostatic control of endocrine and metabolic systems after established lactation, as during the period of feed restriction in the present study, organs are well adapted to metabolic and environmental changes. [ABSTRACT FROM AUTHOR]

The liver has an important role in metabolic regulation and control of the somatotropic axis to adapt successfully to physiological and environmental changes in dairy cows. The aim of this study was to investigate the adaptation to negative energy balance (NEB) at parturition and to a deliberately induced NEB by feed restriction at 100 days in milk. The hepatic gene expression and the endocrine system of the somatotropic axis and related parameters were compared between the early and late NEB period. Fifty multiparous cows were subjected to 3 periods (1 = early lactation up to 12 wk postpartum, 2 = feed restriction for 3 wk beginning at around 100 days in milk with a feed-restricted and a control group, and 3 = subsequent realimentation period for the feed-restricted group for 8 wk). In period 1, plasma growth hormone reached a maximum in early lactation, whereas insulin-like growth factor-I (IGF-I), leptin, the thyroid hormones, insulin, and the revised quantitative insulin sensitivity check index increased gradually after a nadir in early lactation. Three days after parturition, hepatic mRNA abundance of growth hormone receptor 1A, IGF-I, IGF-I receptor and IGF-binding protein-3 (IGFBP-3) were decreased, whereas mRNA of IGFBP-1 and -2 and insulin receptor were upregulated as compared with wk 3 antepartum. During period 2, feed-restricted cows showed decreased plasma concentrations of IGF-I and leptin compared with those of control cows. The revised quantitative insulin sensitivity check index was lower for feed-restricted cows (period 2) than for control cows. Compared with the NEB in period 1, the changes due to the deliberately induced NEB (period 2) in hormones were less pronounced. At the end of the 3-wk feed restriction, the mRNA abundance of IGF-I, IGFBP-1, -2, -3, and insulin receptor was increased as compared with the control group. The different effects of energy deficiency at the 2 stages in lactation show that the endocrine regulation changes qualitatively and quantitatively during the course of lactation. [ABSTRACT FROM AUTHOR]

Adiponectin, one of the most abundant adipokines in circulation, is known for its role in regulation of body metabolism. The aim of this study was to evaluate the effects of a negative energy balance (NEB) at 2 stages of lactation (lactational NEB at the onset of lactation and an induced NEB by feed restriction near 100 d of lactation) on circulating adiponectin concentrations. We also investigated the effect of feed restriction on adiponectin concentrations in milk and the relationships of blood and milk adiponectin with selected plasma or milk variables and with measures of body condition. Plasma adiponectin was measured in 50 multiparous Holstein dairy cows throughout 3 experimental periods [i.e., period 1 = 3 wk antepartum up to 12 wk postpartum, period 2 = 3 wk of feed restriction starting at around 100 d in milk with a control (n = 25) and feed-restricted group (50% of energy requirements; n = 25), and period 3 = subsequent realimentation period for 8 wk]. Milk adiponectin was investigated among 21 multiparous cows at wk 2 and wk 12 of period 1 and wk 2 of period 2. Adiponectin concentrations in plasma and skim milk were measured using an in-house ELISA specific for bovine adiponectin. Major changes in circulating adiponectin concentrations were observed during the periparturient period, whereas energy deficiency during established lactation at around 100 d in milk and subsequent refeeding did not affect plasma adiponectin. Together with lower adiponectin concentrations in milk (µg/mL), the reduction in milk yield led to decreased adiponectin secretion via milk (mg/d) at the second week of feed restriction. Irrespective of time and treatment, milk adiponectin represented about 0.002% of total milk protein. Mean adiponectin concentrations in milk (0.61 ± 0.03 µg/mL) were about 92% lower than the mean plasma adiponectin concentrations (32.1 ± 1.0 µg/mL). The proportion of the steady-state plasma adiponectin pool secreted daily via milk was 2.7%. In view of the similar extent of NEB in both periods of energy deficiency, decreasing adiponectin concentrations seems important for accomplishing the adaptation to the rapidly increasing metabolic rates in early lactation, whereas the lipolytic reaction toward feed restriction-induced NEB during established lactation seems to occur largely independent of changes in circulating adiponectin. [ABSTRACT FROM AUTHOR]

The objective of this study was to improve knowledge regarding the amino acid profile of the insoluble portion of ingested forage escaping rumen degradation. Six forage categories were analyzed. Categories varied in botanical composition and each contained 2 samples. Samples within categories were derived from the same parent material but differed in harvest, maturity, or conservation type. The rumen-undegradable protein of all forages was measured by incubation for 16 h in the rumen of 3 nonlactating cows. All residues were corrected for microbial colonization. The AA profile of the residue was different to the original profile. Degradation trends of individual AA, in terms of increase or decrease relative to the original concentration, were similar between all forages. The AA profiles of forage residues, both within and between categories, were more similar to each other than to their respective original profile. This information may aid in improving the accuracy of estimating postruminal AA supply from forages while decreasing the number of samples required to be analyzed. [ABSTRACT FROM AUTHOR]

In the liver of dairy cows, the production of cytokines is enhanced during the periparturient phase, which in turn leads to inflammation and an impairment of hepatic function. Nuclear factor E2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that controls the transcription of genes encoding various antioxidative and cytoprotective proteins. In the present study, we investigated the hypothesis that Nrf2 is activated in the liver of dairy cows during the periparturient phase to protect the liver against the deleterious effects of cytokines and reactive oxygen species. Therefore, we determined relative mRNA abundances of TNF (encoding tumor necrosis factor-α), various acute phase proteins and several Nrf2 target genes in liver biopsy samples of 20 dairy cows at each time point from 3 wk antepartum to 1, 5, and 14 wk postpartum. We observed an increase in mRNA abundances of TNF and acute-phase proteins [serum amyloid A 3 (SAA3), haptoglobin (HP), and Creactive protein (CRP)] from 3 wk antepartum to 1 wk postpartum, indicative of a proinflammatory condition. Messenger RNA abundances of various Nrf2 target genes with antioxidative or cytoprotective functions [glutathione peroxidase 3 (GPX3); microsomal glutathione S-transferase 3 (MGST3); superoxide dismutase (SOD1); catalase (CAT); metallothioneins 1A, 1E, and 2A (MT1A, MT1E, and MT2A, respectively); NAD(P) H dehydrogenase, quinone 1 (NQO1); heme oxygenase 2 (HMOX2); and UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1)] were also greatly increased from 3 wk antepartum to 1 wk postpartum. From 1 wk postpartum to later lactation, mRNA abundances of all the Nrf2-target genes considered declined but remained at levels that were higher than those in 3 wk antepartum. No correlations were found, however, between plasma concentrations of nonesterified fatty acids or β-hydroxybutyrate and mRNA abundances of Nrf2 target genes, indicating that a negative energy balance might not have been the main factor responsible for upregulation of those genes in the liver during early lactation. In conclusion, this study provides additional evidence that the periparturient phase in dairy cows is associated with a proinflammatory condition in the liver. Moreover, it is shown for the first time that the transition from pregnancy to lactation leads to a strong upregulation of Nrf2 target genes with antioxidative or cytoprotective properties, which might be another physiologic means to prevent the liver against damage by the inflammation process and an increased generation of reactive oxygen species. [ABSTRACT FROM AUTHOR]

Supplementation of conjugated linoleic acids (CLA) reduces milk fat content in dairy cows and, thus, may be a useful dietary strategy to improve energy balance during early lactation. The present study was performed to investigate whether supplementation of CLA could have adverse effects on hepatic lipid metabolism such as observed in rodents. For this aim, 40 Holstein cows were allotted to 2 groups, which were fed daily 172 g of either a CLA-free, rumen-protected control fat (control group) or a rumen-protected CLA fat supplying 4.3 g of cis-9,trans-11 CLA and 3.8 g of trans-10,cis-12 CLA per day (CLA group). To identify potential changes of lipid metabolism, expression of several genes involved in lipid metabolism was determined in liver biopsy samples taken at wk 5 of lactation, using a whole-genome gene chip. In the CLA group, milk fat content and daily milk fat yield were lower than in the control group. Milk yield was higher, whereas fat-corrected milk and energy-corrected milk were lower in the CLA group than in the control group. The CLA group, moreover, had an improved energy balance. To study potential effects of CLA on hepatic lipid metabolism, we considered 6 genes encoding fatty acid transporters, 7 genes involved in intracellular fatty acid transport, 21 and 7 genes, respectively, involved in mitochondrial and peroxisomal β-oxidation, 6 genes of carnitine metabolism, 3 genes of ketogenesis, 21 genes involved in fatty acid and triacylglycerol synthesis, 17 genes involved in cholesterol metabolism, and 20 genes involved in lipoprotein metabolism. None of these genes was differentially regulated between the CLA group and the control group. Gene chip data were confirmed by quantitative PCR analysis, which revealed no difference in the expression of key enzymes of various pathways such as lipogenesis, β-oxidation, and ketogenesis between the 2 groups of cows. In line with those findings, concentrations of triacylglycerols and cholesterol in liver and plasma were not different between the 2 groups of cows. In conclusion, the present study shows that CLA supplementation at a dose effective for milk fat depression does not induce adverse effects on hepatic lipid metabolism in dairy cows. [ABSTRACT FROM AUTHOR]

This study was performed to investigate changes in expression level of genes involved in hepatic cholesterol metabolism in the transition from pregnancy to lactation and during different stages of lactation in dairy cows. Therefore, relative mRNA abundances of several genes involved in various pathways of cholesterol homeostasis in liver biopsy samples of 20 dairy cows, taken in late pregnancy (3 wk prepartum) and early lactation (1, 5, and 14 wk postpartum), were determined. At 1 wk postpartum, hepatic mRNA abundances of genes involved in cholesterol synthesis (3-hydroxy-3-methylglutaryl-coenzyme A reductase, mevalonate kinase, and farnesyl diphosphate synthase), cholesterol uptake from blood (low-density lipoprotein receptor), bile acid synthesis (cholesterol-7α-hydroxylase), cholesterol efflux [ATP-binding cassette (ABC) transporter A1 and ABCG1], esterification of cholesterol (acyl-coenzyme A:cholesterol acyltransferase), and proteins involved in assembly and secretion of very low-density lipoproteins (microsomal triglyceride transfer protein, ApoB100) were increased compared with 3 wk prepartum. The mRNA abundances of most of these genes decreased after 1 wk of lactation and reached levels in 5 and 14 wk of lactation similar to those at 3 wk prepartum. Only mRNA abundances of cholesterol-7α-hydroxylase, ABC transporters, and ApoB100 remained at 5 and 14 wk postpartum at levels higher than those at 3 wk prepartum. Hepatic cholesterol abundance was highest at 1 wk postpartum and was, thereafter, decreasing to values similar to that at 3 wk prepartum. Overall, this study shows that the onset of lactation is associated with an increased expression of various genes involved in cholesterol metabolism in the liver of dairy cows, suggesting that pronounced changes in hepatic cholesterol metabolism take place in the periparturient phase. [ABSTRACT FROM AUTHOR]