Department of Animal Science, Cornell University, Ithaca, NY 14853.
Department of Animal Science, Cornell University, Ithaca, NY 14853.
J Dairy Sci. 2023 Nov;106(11):8122-8132. doi: 10.3168/jds.2023-23373. Epub 2023 Aug 23.
The transition from late pregnancy (LP) to early lactation (EL) in dairy cows is characterized by a major reorganization of the metabolic activities of liver and adipose tissue in support of milk synthesis. This reorganization has been attributed in large part to variation in the plasma concentration and actions of growth hormone, insulin, and other metabolic hormones. A role for the immune system has also been suggested by a near-universal rise in circulating levels of liver-derived acute-phase proteins (APP) in early lactating cows. However, less attention has been devoted to the possibility that resident macrophages of liver and adipose tissue adopt a proinflammatory state (referred herein as inflammatory tone) in parallel with the rise in plasma APP. We addressed this question by measuring the expression of genes expressed predominantly in the resident macrophage population of liver and adipose tissue and indicative of a proinflammatory (tumor necrosis factor α, IL-6, IL-12, resistin, and cluster of differentiation 80 [CD80]) or anti-inflammatory state (IL-10 and chitinase-3-like protein 1 [CHI3L1]). In a first group of cows, none of these inflammatory gene markers were regulated in liver between LP on d -29 (relative to parturition) and on d 8 of EL despite 1.7 to 5.6-fold upregulation in the expression of the APP (haptoglobin, serum amyloid α, and orosomucoid 1). In a second group of healthy cows, expression of the inflammatory gene markers did not differ between livers with low (<5.3%) or high (>11.5%) triglyceride content on d 7 of EL. In adipose tissue, a modest increase in inflammatory tone was suggested between LP and EL by increased CD80 expression and decreased CHI3L1 expression in EL. To assess the possibility that inflammatory tone would be more prominent if assayed in a cell compartment enriched with macrophages, adipose tissue was obtained in LP on d -28 and in EL on d +10 from cows experiencing a healthy transition period and fractionated into its adipocyte and stromal vascular cell (SVC) compartments. Expression of inflammatory gene markers was higher in SVC than adipocytes but remained unregulated in SVC between LP and EL. Overall, these results suggest little change in the inflammatory tone of resident macrophages in liver and adipose tissue of healthy transition dairy cows and do not support a role for the local immune system in the reorganization of metabolism in these tissues at the onset of lactation.
奶牛从妊娠后期(LP)向泌乳早期(EL)的过渡以肝脏和脂肪组织代谢活动的重大重组为特征,以支持牛奶的合成。这种重组在很大程度上归因于生长激素、胰岛素和其他代谢激素的血浆浓度和作用的变化。循环中肝脏来源的急性期蛋白(APP)水平的普遍升高也表明免疫系统发挥了作用,早期泌乳奶牛中普遍存在这种情况。然而,人们对驻留于肝脏和脂肪组织的巨噬细胞是否可能与血浆 APP 升高平行而呈现促炎状态(本文中称为炎症状态)关注较少。我们通过测量肝脏和脂肪组织中驻留巨噬细胞群体中主要表达的基因的表达来解决这个问题,这些基因的表达表明促炎(肿瘤坏死因子-α、IL-6、IL-12、抵抗素和分化群 80[CD80])或抗炎状态(IL-10 和几丁质酶-3 样蛋白 1[CHI3L1])。在第一组奶牛中,尽管 APP(触珠蛋白、血清淀粉样蛋白α和乳白蛋白 1)的表达上调了 1.7 至 5.6 倍,但在 LP 至 EL 的第 29 天(相对于分娩)之间,肝脏中没有这些炎症基因标志物受到调节。在第二组健康奶牛中,EL 第 7 天肝脏中甘油三酯含量较低(<5.3%)或较高(>11.5%)时,炎症基因标志物的表达没有差异。在脂肪组织中,EL 中 CD80 表达增加和 CHI3L1 表达减少提示 LP 和 EL 之间炎症状态略有增加。为了评估在富含巨噬细胞的细胞区室中检测时炎症状态是否会更加明显,我们从经历健康过渡期的奶牛中获得 LP 时的第-28 天和 EL 时的第 10 天的脂肪组织,并将其分离成脂肪细胞和基质血管细胞(SVC)区室。与脂肪细胞相比,SVC 中的炎症基因标志物表达更高,但在 LP 和 EL 之间 SVC 中的表达仍未调节。总体而言,这些结果表明,健康过渡奶牛的肝脏和脂肪组织中驻留巨噬细胞的炎症状态几乎没有变化,并且不支持局部免疫系统在泌乳开始时这些组织代谢重排中的作用。