Long-term molecular adaptations in liver from high-producing dairy cows are virtually unknown. Liver from five Holstein cows was biopsied at -65, -30, -14, +1, +14, +28, and +49 days relative to parturition for transcript profiling using a microarray consisting of 7,872 annotated cattle cDNA inserts. More than 5,000 cDNA elements represented on the microarray were expressed in liver. From this set we identified 62 differentially expressed genes related to physiological state, with a false discovery rate threshold of P = 0.20. The dominant expression pattern consisted of upregulation from day -30 through day +1, followed by downregulation through day +28. There was a threefold decrease from day -65 through day +14 in expression of IGFBP3, GSTM5, and PDPK1. These genes mediate IGF-I transport, oxidative stress, and glucose homeostasis, respectively. IGFBP3, EIF4B, and GSTM5 mRNA levels were positively correlated with blood serum total protein. Correlation analysis showed positive associations between serum nonesterified fatty acids and mRNA expression for SAA1, CPT1A, ACADVL, and TFAP2A. Transcript levels of ACSL1, PPARA, and TFAP2A were positively correlated with serum beta-hydroxybutyrate. Expression patterns for certain genes (e.g., IGFBP3, HNF4A, GPAM) revealed adaptations commencing well ahead of parturition, suggesting they are regulated by factors other than periparturient hormonal environment. Results provide evidence that hepatic inflammatory responses occurring near parturition initiate or augment adipose catabolism. In this context, cytokines, acute-phase proteins, and serum nonesterified fatty acids are key players in periparturient cow metabolism. We propose a model for integrating gene expression, metabolite, and liver composition data to explain physiological events in placenta, adipose, and liver during the periparturient period.

Dairy cows undergo tremendous metabolic and physiological adaptations around parturition to support lactation. The liver 

is central to many of these processes, including gluconeogenesis and metabolism of fatty acids mobilized from adipose tis- 

sue. Fat accumulation may impair normal functions of the liver and increase ketogenesis, which in turn may predispose cows 

to other metabolic abnormalities. Several aspects of dietary management and body condition may alter these adaptations, 

affect dry matter intake, and increase or decrease susceptibility to periparturient health problems. Overfeeding energy dur- 

ing the dry period is a prominent risk factor. Considerable progress has been made in recent years in describing the adap- 

tive changes in the liver and other organs in normal and abnormal states, but this knowledge has not yet identified unequiv- 

ocally the key steps that might be compromised during development of metabolic disorders. The potential role of signaling 

compounds, such as the inflammatory cytokines released in response to environmental stressors, infectious challenge, and 

oxidative stress, in the pathogenesis of periparturient disease is under investigation. New techniques such as functional 

genomics, using cDNA or oligonucleotide microarrays, as well as proteomics and metabolomics, provide additional high- 

throughput tools to determine the effects of nutrition, management, or stressors on tissue function in development of dis- 

ease. Integrative approaches should be fruitful in unraveling the complex interactions of metabol...

Liver metabolism and health in dairy cows during the periparturient period are affected by plane of nutrition prepartum. Long-term adaptations in hepatic gene expression are important for complete understanding of liver function. We examined temporal gene expression profiles during the dry period and early lactation in liver of Holstein cows fed moderate dietary energy ad libitum or restricted during the entire dry period using a microarray consisting of 7,872 annotated cattle cDNA inserts and quantitative RT-PCR. We identified 85 genes with expression patterns that were affected by level of energy intake prepartum over time. Restricted energy intake prepartum resulted in more pronounced upregulation of genes with key functions in hepatic fatty acid oxidation (CPT1A, ADIPOR2), gluconeogenesis (PC), and cholesterol synthesis (SC4MOL). Ad libitum feeding upregulated a number of genes associated with liver triacylglycerol synthesis (DGAT1) and proinflammatory cytokines (TNFAIP3). Genomic responses to ad libitum feeding were accompanied by increased incorporation of palmitate to esterified products in vitro and increased liver triacylglycerol concentration in vivo. Overall, gene expression profiles due to plane of nutrition prepartum partly explained differences in rates of liver palmitate metabolism, blood serum metabolite concentrations, and liver tissue triacylglycerol concentration. Our data show that moderate overfeeding of energy in the dry period, in the absence of obesity, results in transcriptional changes predisposing cows to fatty liver and perhaps compromising overall liver health during the periparturient period. In this context, controlled energy intake may confer an advantage to the cow by triggering hepatic molecular adaptations well ahead of parturition.

Choline is important for assembly of very low density lipoproteins to export triglyceride from liver; however, studies to assess the effect of rumen-protected choline (RPC) supplementation on blood lipid metabolites in periparturient dairy cows have not been conducted. Thirty-two multiparous Holstein and 10 multiparous Jersey cows were randomly assigned to control or RPC treatments. A close-up diet was fed from approximately 3 wk before parturition through parturition, followed by a lactation diet from parturition through 49 d postpartum. For RPC, diets were top-dressed once daily with 60 g of a RPC product (25% choline as choline chloride) from 21 d before expected parturition through 21 d postpartum. Treatment did not affect dry matter intake either prepartum (12.0 vs. 12.1 kg/d for RPC and control, respectively) or during the first 3 wk postpartum (14.8 vs. 15.7 kg/d, respectively). Daily yields of 3.5% fat-corrected milk (39.4 vs. 37.4 kg/d), fat (1.46 vs. 1.38 kg/d), and protein (1.09 vs. 1.05 kg/d) did not differ statistically by treatment (RPC vs. control, respectively). Jersey cows in the control group had lower concentrations of nonesterified fatty acids and beta-hydroxybutyrate in plasma during d 1 to 10 postpartum than did other breed and treatment combinations. Cows fed RPC tended to have greater serum triglycerides prepartum (17.0 vs. 14.7 mg/dL) and lower plasma phospholipid at parturition (65.2 vs. 78.1 mg/dL) than control cows. Treatment did not affect cholesterol and phospholipid at other time points, but concentrations followed patterns of dry matter intake pre- and postpartum. Cows were in moderate body condition score (mean = 3.3) at the start of the study and did not lose excessive condition by 3 wk postpartum (mean body condition score loss = 0.5); therefore, cows might not have been at great risk for hepatic lipid accumulation. Additionally, calculated Met balance was negative postpartum; supplemental RPC might not have spared enough Met to produce a physiological benefit. More research is needed to determine how choline affects prevention or alleviation of fatty liver syndrome and to confirm potential differences between Holstein and Jersey cows.