Hepatic transcriptomic adaptation from prepartum to postpartum in dairy cows

Abstract

The transition from pregnancy to lactation is the most challenging period for high-producing dairy cows. The liver plays a key role in biological adaptation during the peripartum. Prior works have demonstrated that hepatic glucose synthesis, cholesterol metabolism, lipogenesis, and inflammatory response are increased or activated during the peripartum in dairy cows; however, those works were limited by a low number of animals used or by the use of microarray technology, or both. To overcome such limitations, an RNA sequencing analysis was performed on liver biopsies from 20 Holstein cows at 7 ± 5d before (Pre-P) and 16 ± 2d after calving (Post-P). We found 1,475 upregulated and 1,199 downregulated differently expressed genes (DEG) with a false discovery rate adjusted P-value < 0.01 between Pre-P and Post-P. Bioinformatic analysis revealed an activation of the metabolism, especially lipid, glucose, and amino acid metabolism, with increased importance of the mitochondria and a key role of several signaling pathways, chiefly peroxisome proliferators-activated receptor (PPAR) and adipocytokines signaling. Fatty acid oxidation and gluconeogenesis, with a likely increase in amino acid utilization to produce glucose, were among the most important functions revealed by the transcriptomic adaptation to lactation in the liver. Although gluconeogenesis was induced, data indicated decrease in expression of glucose transporters. The analysis also revealed high activation of cell proliferation but inhibition of xenobiotic metabolism, likely due to the liver response to inflammatory-like conditions. Co-expression network analysis disclosed a tight connection and coordination among genes driving biological processes associated with protein synthesis, energy and lipid metabolism, and cell proliferation. Our data confirmed the importance of metabolic adaptation to lipid and glucose metabolism in the liver of early Post-P cows, with a pivotal role of PPAR and adipocytokines.

Peroxisome Proliferator-Activated Receptor Activation in Precision-Cut Bovine Liver Slices Reveals Novel Putative PPAR Targets in Periparturient Dairy Cows

“…Though the library prep kit used is apt at maximizing sequencing depth when compared with other commercial solutions, we noticed that many transcripts with (typically) a relatively low expression were either not detected or detected at very low level, with zero-counts in most samples. Despite being able to detect >14,000 transcripts with a count>4 in at the least one sample, which is somewhat similar to what previously reported in RNAseq analysis of bovine liver (125)(126)(127), many transcripts with a relatively medium-low expression were either not detected or detected at very low level, with lack of detection in most samples. Most of the genes used for the RT-qPCR were in this category, such as all PPAR transcripts and LIPC.…”

The Overlooked Transformation Mechanisms of VLCFAs: Peroxisomal β-Oxidation

“…One of the significant roles it plays in dairy cows from the point of view of economic interest is controlling the synthesis of milk fat in dairy cows, not only in mitochondria but also with ELVOL participating in the regulation of peroxisomal β-oxidation. PPARγ expression increases during changes in the lactation period [55,56], thereby regulating peroxisomal β-oxidation to prevent metabolic stress. Research further confirmed the importance of PPARγ in regulating milk fat production [57,58].…”

The mechanistic target of rapamycin complex 1 pathway involved in hepatic gluconeogenesis through peroxisome-proliferator-activated receptor γ coactivator-1α

“…We speculate the functioning of the transcription factor not only depends on its quantity but is also determined by its activity and intracellular location. Similarly, even though it is well recognized that PPAR has an important role in the adaptation of the liver to the transition period in dairy cows, the gene or protein expression of its isotypes such as PPARA (the gene symbol of PGC-1 α ) and PPARG had no significant changes during the transition period ( Bionaz et al., 2015 ; Gao et al., 2021 ; Schaff et al., 2012 ). Therefore, although the transcription level of PGC-1 α has not been improved, its activation and location may be regulated by post-translational modification, which may involve the regulation of protein kinase mTORC1 ( Cunningham et al., 2007 ).…”