Plane of nutrition pre-partum alters hepatic gene expression

21 Liver metabolism and health in dairy cows during the periparturient period are affected 22 by plane of nutrition pre-partum. Long-term adaptations in hepatic gene expression are 23 important for complete understanding of liver function. We examined temporal gene expression 24 profiles during the dry period and early lactation in liver of Holstein cows fed moderate dietary 25 energy ad libitum or restricted during the entire dry period using a microarray consisting of 7,872 26 annotated cattle cDNA inserts and quantitative RT-PCR. We identified 85 genes with expression 27 patterns that were affected by level of energy intake pre-partum over time. Restricted energy 28 intake pre-partum resulted in more pronounced up-regulation of genes with key functions in 29 hepatic fatty acid oxidation (CPT1A, ADIPOR2), gluconeogenesis (PC), and cholesterol 30 synthesis (SC4MOL). Ad libitum feeding up-regulated a number of genes associated with liver 31 triacylglycerol synthesis (DGAT1) and pro-inflammatory cytokines (TNFAIP3). Genomic 32 responses to ad libitum feeding were accompanied by increased incorporation of palmitate to 33 esterified products in vitro and increased liver triacylglycerol concentration in vivo. Overall, 34 gene expression profiles due to plane of nutrition pre-partum partly explained differences in rates 35 of liver palmitate metabolism, blood serum metabolite concentrations, and liver tissue 36 triacylglycerol concentration. Our data show that moderate overfeeding of energy in the dry 37 period, in the absence of obesity, results in transcriptional changes predisposing cows to fatty 38 liver and perhaps compromising overall liver health during the periparturient period. In this 39 context, controlled energy intake may confer an advantage to the cow by triggering hepatic 40 molecular adaptations well ahead of parturition. 41 42