During the transition from late gestation to early lactation ruminants experience a negative energy balance (NEB), which is considered to increase susceptibility to mammary infections. Our previous study in 2 divergent lines of sheep selected for high and low somatic cell score (SCS) suggested an association between the response to NEB and genetic susceptibility to mastitis. Forty-eight early-lactation primiparous dairy ewes from the 2 SCS genetic lines were allocated to 2 homogeneous subgroups—an NEB group, which was energy restricted and received 60% of the energy requirements for 15 d, and a control-fed group—to obtain 4 balanced groups of 12 ewes: high-SCS positive energy balance, low-SCS positive energy balance, high-SCS NEB, and low-SCS NEB. High-SCS ewes showed greater weight loss and increased plasmatic concentrations of β-hydroxybutyrate and nonesterified fatty acids than low-SCS ewes when confronted with an induced NEB. The aim of this study was to further characterize this interaction by combining transcriptomic and phenotypic data with a generalized partial least squares discriminant analysis using mixOmics package framework. A preliminary analysis using 3 blocks of phenotypes (fatty acids, weight and production, blood metabolites) revealed a high correlation between fat-to-protein ratio, β-hydroxybutyrate, and nonesterified fatty acids concentrations with milk long-chain fatty acid yields. These phenotypes allowed good discrimination of the energy-restricted high-SCS ewes and confirmed a high level of adipose tissue mobilization in this group. A second analysis, which included RNA-seq data, revealed high correlations between the long-chain fatty acid yields in milk and PDK4, CPT1A, SLC25A20, KLF10, and KLF11 expression, highlighting the relationship between mobilization of body reserves and enhanced fatty acids utilization for energy production in blood cells. Finally, analysis of milk composition measured in 1,025 ewes from the 2 genetic lines over 10 yr confirmed significant higher fat-to-protein ratio in high-SCS ewes in early lactation. Altogether, our results strongly confirmed a genetic link between susceptibility to mastitis and metabolic adaptation to energy shortage. Improving genetic resistance to mastitis using SCS should be accompanied by a favorable effect on the response to metabolic stress, especially in highly stressful early lactation. Moreover, this study suggests that the fat-to-protein ratio could be used as a low-cost tool for monitoring energy balance and ketosis during this critical phase of lactation.

在从妊娠后期到哺乳期的过渡过程中，反刍动物会出现负能量平衡（NEB），这被认为会增加对乳腺感染的易感性。我们先前对2种不同的绵羊品系进行的研究选择了高和低的体细胞评分（SCS），表明对NEB的反应与对乳腺炎的遗传易感性之间存在关联。将来自2个SCS基因系的48个早期泌乳初生母羊分配给2个同质亚组，即NEB组，该组能量受限，在15 d内接受60％的能量需求，而对照组则为对照组。获得12个母羊的4组平衡组：高SCS正能量平衡，低SCS正能量平衡，高SCS NEB和低SCS NEB。与低SCS母羊面对诱导的NEB相比，高SCS母羊显示出更大的体重减轻和血浆中β-羟基丁酸酯和非酯化脂肪酸的浓度增加。这项研究的目的是通过将转录组和表型数据与使用mixOmics软件包框架进行的广义偏最小二乘判别分析相结合，进一步表征这种相互作用。使用3种表型（脂肪酸，重量和产量，血液代谢物）的初步分析显示，脂肪与蛋白质的比率，β-羟基丁酸酯和非酯化脂肪酸浓度与牛奶长链脂肪酸产量之间存在高度相关性。这些表型可以很好地区分能量受限的高SCS母羊，并证实该组脂肪组织的动员水平很高。第二个分析PDK4，CPT1A，SLC25A20，KLF10和KLF11表达，突出了动员身体储备和提高脂肪酸在血细胞中产生能量之间的关系。最后，在10年的时间里，从这2个遗传系的1,025头母羊中测得的牛奶成分分析证实，高SCS母羊在泌乳早期脂肪/蛋白质比率显着更高。总之，我们的结果强烈证实了对乳腺炎的易感性和对能量缺乏的代谢适应之间的遗传联系。使用SCS提高对乳腺炎的遗传抗性应伴随对代谢应激反应的有利作用，尤其是在高应激早期哺乳期。此外，这项研究表明，脂肪与蛋白质的比例可以用作在泌乳这个关键阶段监测能量平衡和酮症的低成本工具。