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妊娠末期过度饲养对奶牛肝脏整体基因表达模式的影响。

Effect of overconditioning on the hepatic global gene expression pattern of dairy cows at the end of pregnancy.

机构信息

Department of Reproduction, Obstetrics and Herd Health, Faculty of Veterinary Medicine, Ghent University, 9820 Merelbeke, Belgium; Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, 2610 Wilrijk, Belgium.

Department of Reproduction, Obstetrics and Herd Health, Faculty of Veterinary Medicine, Ghent University, 9820 Merelbeke, Belgium.

出版信息

J Dairy Sci. 2021 Jul;104(7):8152-8163. doi: 10.3168/jds.2020-19302. Epub 2021 Apr 23.

DOI:10.3168/jds.2020-19302
PMID:33896624
Abstract

Overconditioning is a risk factor for upregulated pre- and postpartum fat mobilization. Therefore, we hypothesized that overconditioning at the end of pregnancy leads to the accumulation of lipids in the liver and modifications of the hepatic gene expression pattern. The aim of this study was to evaluate the effect of normal- versus overconditioning on the hepatic transcriptomic profile of dairy cows at the end of pregnancy. Ten dry multiparous Holstein cows were killed 2 wk before expected calving. Body condition score (BCS) and backfat thickness (BFT) were evaluated, and blood samples for nonesterified fatty acids (NEFA) were taken before cows were killed. After cows were killed, liver biopsy samples were collected for further assessment of total lipids and RNA sequencing. Five cows were classified as normal-conditioned (median BCS = 3, range 2.75-3.5) and 5 as overconditioned (median BCS = 4, range 4-5). Regression models confirmed that normal-conditioned cows had lower BFT (1.29 ± 0.29 cm; least squares means ± standard error) and serum NEFA (0.16 ± 0.04 mmol/L) in comparison to overconditioned cows (3.14 ± 0.43 cm and 0.38 ± 0.07 mmol/L for BFT and NEFA, respectively). Total liver lipid percentage tended to be lower in normal- versus overconditioned cows (4.63 ± 0.40% and 6.06 ± 0.44%, respectively). In comparison to the mean liver lipid percentage of the normal- and overconditioned cows, 1 overconditioned cow had a relatively low (5.21%) and 1 normal-conditioned cow had a relatively high (6.07%) liver lipid percentage. Differentially expressed genes analysis (edgeR quasi-likelihood method) showed that normal-conditioned cows presented 11 upregulated and 12 downregulated genes in comparison to overconditioned cows. Linear discriminant analysis effects size revealed 133 differentially expressed genes between normal- versus overconditioned cows. Notably, the liver of normal-conditioned cows had upregulated genes associated with liver functionality (ALB, SELENOP, IGF1, and IGF2). On the other hand, overconditioned cows had upregulated genes associated with the acute-phase response (C3, HPX, and, LBP). High basal lipolysis in overconditioned cows at the end of pregnancy increased liver lipid content, and this may alter the hepatic gene expression pattern to a pro-inflammatory state.

摘要

过度饲养是妊娠前后脂肪动员上调的一个风险因素。因此,我们假设在妊娠末期过度饲养会导致肝脏脂质积累和肝基因表达模式的改变。本研究旨在评估正常饲养与过度饲养对妊娠末期奶牛肝脏转录组谱的影响。10 头干多胎荷斯坦奶牛在预计分娩前 2 周被处死。在奶牛被处死前,评估体况评分(BCS)和背膘厚度(BFT),并采集非酯化脂肪酸(NEFA)的血液样本。奶牛死后,采集肝活检样本进行进一步评估总脂质和 RNA 测序。将 5 头奶牛分为正常饲养组(BCS 中位数为 3,范围 2.75-3.5),5 头奶牛分为过度饲养组(BCS 中位数为 4,范围 4-5)。回归模型证实,与过度饲养组相比,正常饲养组奶牛的 BFT(1.29±0.29cm;最小二乘均值±标准误差)和血清 NEFA(0.16±0.04mmol/L)较低。与正常饲养组相比,过度饲养组奶牛的总肝脂质百分比也较低(分别为 4.63±0.40%和 6.06±0.44%)。与正常和过度饲养组奶牛的平均肝脂质百分比相比,1 头过度饲养组奶牛的肝脂质百分比相对较低(5.21%),1 头正常饲养组奶牛的肝脂质百分比相对较高(6.07%)。差异表达基因分析(edgeR 拟似然方法)显示,与过度饲养组相比,正常饲养组奶牛有 11 个上调和 12 个下调基因。线性判别分析效应大小显示,正常饲养组与过度饲养组奶牛之间有 133 个差异表达基因。值得注意的是,正常饲养组奶牛的肝脏中上调的基因与肝脏功能有关(ALB、SELENOP、IGF1 和 IGF2)。另一方面,过度饲养组奶牛上调的基因与急性期反应有关(C3、HPX 和 LBP)。过度饲养组奶牛在妊娠末期基础脂解作用增强,导致肝脏脂质含量增加,这可能改变肝脏基因表达模式,使其向炎症状态转变。

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