State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.
Department of Animal and Rangeland Sciences, Oregon State University, Corvallis 97331.
J Dairy Sci. 2021 Jan;104(1):1053-1072. doi: 10.3168/jds.2020-19101. Epub 2020 Nov 12.
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.
从妊娠到泌乳的过渡是高产奶牛最具挑战性的时期。肝脏在围产期的生物适应中起着关键作用。先前的研究已经证明，在围产期奶牛的肝脏中，葡萄糖合成、胆固醇代谢、脂肪生成和炎症反应增加或被激活；然而，这些研究受到所使用动物数量少或使用微阵列技术或两者兼有的限制。为了克服这些限制，对 20 头荷斯坦奶牛的肝脏活检进行了 RNA 测序分析，这些奶牛在产犊前 7±5 天（Pre-P）和产犊后 16±2 天（Post-P）采集样本。我们发现 Pre-P 和 Post-P 之间有 1475 个上调和 1199 个下调的差异表达基因（DEG），假发现率调整后的 P 值<0.01。生物信息学分析显示，代谢，特别是脂质、葡萄糖和氨基酸代谢被激活，线粒体的重要性增加，几个信号通路起关键作用，主要是过氧化物酶体增殖物激活受体（PPAR）和脂肪细胞因子信号通路。脂肪酸氧化和糖异生，可能增加氨基酸的利用来产生葡萄糖，是肝脏对泌乳的转录组适应所揭示的最重要的功能之一。尽管糖异生被诱导，但数据表明葡萄糖转运蛋白的表达减少。该分析还显示细胞增殖的高度激活，但对异生物质代谢的抑制，可能是由于肝脏对炎症样条件的反应。共表达网络分析揭示了与蛋白质合成、能量和脂质代谢以及细胞增殖相关的生物学过程的基因之间的紧密联系和协调。我们的数据证实了代谢适应对肝脏脂质和葡萄糖代谢的重要性，PPAR 和脂肪细胞因子起着关键作用。
