Zarrin M, Wellnitz O, van Dorland H A, Gross J J, Bruckmaier R M
Veterinary Physiology, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109a, 3001 Bern, Switzerland; Department of Animal Science, Agriculture Faculty, Yasouj University, Student Street, 75918-74831, Yasouj, I. R. Iran; Graduate School for Cellular and Biomedical Sciences, University of Bern, Freiestrasse 1, 3012 Bern, Switzerland.
Veterinary Physiology, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109a, 3001 Bern, Switzerland.
J Dairy Sci. 2014;97(6):3531-41. doi: 10.3168/jds.2013-7480. Epub 2014 Mar 27.
Hyperketonemia interferes with the metabolic regulation in dairy cows. It is assumed that metabolic and endocrine changes during hyperketonemia also affect metabolic adaptations during inflammatory processes. We therefore studied systemic and local intramammary effects of elevated plasma β-hydroxybutyrate (BHBA) before and during the response to an intramammary lipopolysaccharide (LPS) challenge. Thirteen dairy cows received intravenously either a Na-DL-β-OH-butyrate infusion (n = 5) to achieve a constant plasma BHBA concentration (1.7 ± 0.1 mmol/L), with adjustments of the infusion rates made based on immediate measurements of plasma BHBA every 15 min, or an infusion with a 0.9% NaCl solution (control; n = 8) for 56 h. Infusions started at 0900 h on d 1 and continued until 1700 h 2 d later. Two udder quarters were challenged with 200 μg of Escherichia coli LPS and 2 udder quarters were treated with 0.9% saline solution as control quarters at 48 h after the start of infusion. Blood samples were taken at 1 wk and 2h before the start of infusions as reference samples and hourly during the infusion. Mammary gland biopsies were taken 1 wk before, and 48 and 56 h (8h after LPS challenge) after the start of infusions. The mRNA abundance of key factors related to BHBA and fatty acid metabolism, and glucose transporters was determined in mammary tissue biopsies. Blood samples were analyzed for plasma glucose, BHBA, nonesterified fatty acid, urea, insulin, glucagon, and cortisol concentrations. Differences were not different for effects of BHBA infusion on the mRNA abundance of any of the measured target genes in the mammary gland before LPS challenge. Intramammary LPS challenge increased plasma glucose, cortisol, glucagon, and insulin concentrations in both groups but increases in plasma glucose and glucagon concentration were less pronounced in the Na-DL-β-OH-butyrate infusion group than in controls. In response to LPS challenge, plasma BHBA concentration decreased in controls and decreased also slightly in the BHBA-infused animals because the BHBA concentration could not be fully maintained despite a rapid increase in BHBA infusion rate. The change in mRNA abundance of citrate synthase in LPS quarters was significant between the 2 treatment groups. The results indicate that elevated circulating BHBA concentration inhibits gluconeogenesis before and during immune response to LPS challenge, likely because BHBA can replace glucose as an energy source.
高酮血症会干扰奶牛的代谢调节。据推测，高酮血症期间的代谢和内分泌变化也会影响炎症过程中的代谢适应。因此，我们研究了在对乳房内脂多糖（LPS）刺激作出反应之前和期间，血浆β-羟基丁酸（BHBA）升高对全身和乳房局部的影响。13头奶牛静脉内注射Na-DL-β-羟基丁酸盐（n = 5）以维持恒定的血浆BHBA浓度（1.7±0.1 mmol/L），每15分钟根据血浆BHBA的即时测量结果调整注射速率，或注射0.9%氯化钠溶液（对照组；n = 8），持续56小时。注射于第1天09:00开始，持续至2天后的17:00。在注射开始后48小时，两个乳房象限用200μg大肠杆菌LPS进行刺激，另外两个乳房象限用0.9%盐溶液处理作为对照象限。在注射开始前1周和2小时采集血样作为参考样本，并在注射期间每小时采集一次。在注射开始前1周、48小时和56小时（LPS刺激后8小时）采集乳房组织活检样本。测定乳房组织活检样本中与BHBA和脂肪酸代谢以及葡萄糖转运蛋白相关的关键因子的mRNA丰度。分析血样中的血浆葡萄糖、BHBA、非酯化脂肪酸、尿素、胰岛素、胰高血糖素和皮质醇浓度。在LPS刺激前，BHBA注射对乳房中任何测量的靶基因的mRNA丰度的影响无差异。乳房内LPS刺激使两组的血浆葡萄糖、皮质醇、胰高血糖素和胰岛素浓度均升高，但Na-DL-β-羟基丁酸盐注射组的血浆葡萄糖和胰高血糖素浓度升高幅度小于对照组。对LPS刺激的反应中，对照组的血浆BHBA浓度降低，注射BHBA的动物的血浆BHBA浓度也略有降低，因为尽管BHBA注射速率迅速增加，但BHBA浓度仍无法完全维持。两个治疗组之间，LPS刺激象限中柠檬酸合酶的mRNA丰度变化显著。结果表明，循环中BHBA浓度升高在对LPS刺激的免疫反应之前和期间抑制糖异生，可能是因为BHBA可以替代葡萄糖作为能量来源。
