Prepartal high-energy feeding with grass silage-based diets does not disturb the hepatic adaptation of dairy cows during the periparturient period

Abstract

The liver of dairy cow naturally undergoes metabolic adaptation during the periparturient period in response to the increasing demand for nutrients. The hepatic adaptation is affected by prepartal energy intake level and is potentially associated with inflammatory responses. To study the changes in the liver function during the periparturient period, 16 cows (body condition score = 3.7 ± 0.3, mean ± standard deviation; parity = second through fourth) were allocated to a grass silage-based controlled-energy diet (104 MJ/d) or a high-energy diet (135 MJ/d) during the last 6 wk before the predicted parturition. Liver samples were collected by biopsy at 8 d before the predicted parturition (-8 d) and at 1 and 9 d after the actual parturition (1 and 9 d). The lipidomic profile of liver samples collected at -8 and 9 d was analyzed using ultra performance liquid chromatography-mass spectrometry-based lipidomics. Liver samples from all the time points were subjected to microarray analysis and the subsequent pathway analysis with Ingenuity Pathway Analysis software (Ingenuity Systems, Mountain View, CA). Prepartal energy intake level affected hepatic gene expression and lipidomic profiles prepartum, whereas little or no effect was observed postpartum. At -8 d, hepatic lipogenesis was promoted by prepartal high-energy feeding through the activation of X receptor/retinoid X receptor pathway and through increased transcription of thyroid hormone-responsive (THRSP). Hepatic inflammatory and acute phase responses at -8 d were suppressed (z-score = -2.236) by prepartal high-energy feeding through the increase in the mRNA abundance of suppressor of cytokine signaling 3 (SOCS3) and the decrease in the mRNA abundance of interleukin 1 (IL1), nuclear factor kappa B 1 (NFKB1), apolipoprotein A1 (APOA1), serum amyloid A3 (SAA3), haptoglobin (HP), lipopolysaccharide-binding protein (LBP), and inter-α-trypsin inhibitor heavy chain 3 (ITIH3). Moreover, prepartal high-energy feeding elevated hepatic concentrations of C18- (7%), C20- (17%), C21- (26%), C23-sphingomyelins (26%), and total saturated sphingomyelin (21%). In addition, cows in both groups displayed increased lipogenesis at the gene expression level after parturition and alterations in the concentration of various sphingolipids between the first and last samplings. In conclusion, prepartal high-energy feeding promoted lipogenesis and suppressed inflammatory and acute phase responses in the liver before parturition, whereas only minor effects were observed after parturition.

Hepatic transcriptomic adaptation from prepartum to postpartum in dairy cows

“…During the peripartum period, the ability of the liver to face increased metabolic challenges is a prerequisite for cows' successful adaptation to lactation without development of health disorders (Graber et al, 2010;Ha et al, 2017). Therefore, several studies have been carried out to improve understanding of the biological changes of the liver during the peripartum, using high-throughput transcriptomic techniques (Loor et al, 2005;Ha et al, 2017;Qin et al, 2018).…”

“…The same data set, analyzed using a more robust statistical approach, uncovered that up to 20% of the measured genes were affected by the peripartum in the liver . A work by Qin et al (2018) detected change of 654 DEG (FDR = 0.05) from −8 to 9 d relative to parturition in 16 Holstein cows (with 2 different diets prepartum) using an Affymetrix array (Affymetrix Inc., Santa Clara, CA), corresponding to <5% of unique measured genes. In the work of Ha et al (2017), ~1,000 DEG were detected in the liver of 6 cows, with FDR = 0.05, out of 10,000 measured genes, corresponding to 10% of the measure transcriptome.…”

“…However, most of the prior studies focused on specific aspects (Reynolds et al, 2003;Schlegel et al, 2012) and did not provide a comprehensive view of the adaptation of the liver to lactation even when high-throughput transcriptomic technologies were used, due to limitation of sensitivity typical of microarrays (Loor et al, 2005;Qin et al, 2018) or inadequate power analysis, as when only 6 cows were used per treatment (Ha et al, 2017). Thus, we found a lingering need for a study to comprehensively investigate the transcriptomic adaptation of the liver of dairy cows during the peripartum.…”

“…Because of the key role of the liver in controlling and regulating the metabolic adaptation during the peripartum (Drackley et al, 2005), several studies have been conducted to investigate liver adaptation to lactation. Those studies revealed that the liver during the adaptation to lactation augments the synthesis of glucose (Reynolds et al, 2003), cholesterol metabolism (Schlegel et al, 2012), and lipogenesis (Qin et al, 2018), and becomes more responsive to stimuli that induce inflammation (Loor et al, 2005). In addition, a recent hepatic transcriptomic study using RNA sequencing (RNAseq; Ha et al, 2017) confirmed that major hepatic changes during the peripartum in dairy cows are related to energy metabolism; in particular, they are related to fatty acid oxidation and metabolism, cholesterol metabolism, and gluconeogenesis.…”

Short communication: Enhanced autophagy activity in liver tissue of dairy cows with mild fatty liver

“…A key problem during transition is the tremendous increase in energy requirements for milk production that, paralleled with a decrease in feed intake, drives cows into a state of negative energy balance (NEB). As a result, the liver undergoes important metabolic adaptations designed to accommodate not only the influx of fatty acids but also the need for gluconeogenesis to support milk synthesis (Ha et al, 2017;Qin et al, 2018). Although several adaptive biochemical, transcriptional, and translational mechanisms experienced by the liver during the transition period have been reported (Loor et al, 2013;Imhasly et al, 2015;Du et al, 2018b), much less is known about the underlying mechanisms that allow hepatocytes to cope with the decrease in nutrition supply.…”