Department of Animal Science, Michigan State University, East Lansing 48824.
Department of Animal Science, Michigan State University, East Lansing 48824.
J Dairy Sci. 2019 Sep;102(9):7997-8010. doi: 10.3168/jds.2018-15907. Epub 2019 Jul 3.
The objective of this research was to identify potential short-term metabolic bottlenecks of propionate metabolism in the liver of dairy cows in the postpartum (PP) period and how such bottlenecks are affected by feeding status. Propionate, produced primarily from the fermentation of starch, decreases dry matter intake for cows in the postpartum period, likely by stimulating oxidation of acetyl-CoA in the liver. In this study, 8 dairy cows [2 blocks of 4 cows each, 6.63 ± 1.19 (mean ± SD) days PP; body condition score of 2.84 ± 0.39] were administered a pulse dose of either 1.5 mol/500 mL of propionic acid (PA) or 500 mL of water (control; CON) to the rumen either 1 h before or 2 h after feeding in a 4 × 4 Latin square design with a 2 × 2 factorial arrangement of treatments. Liver tissue was sampled at -1, 10 and 20 min relative to dosing, and blood was sampled at -30, -20, -10, -1, 5, 10, 15, 20, 25, 30, and 60 min relative to dosing. We hypothesized that rapid propionate absorption results in bottlenecks as enzymes become saturated and cofactors require regeneration. The PA treatment increased plasma propionate and insulin concentrations rapidly, with peaks reached by 5 min regardless of feeding status and cleared from the plasma within 30 min of dosing. The PA treatment decreased plasma nonesterified fatty acid concentration over 30 min compared with CON before but not after feeding. The PA treatment decreased plasma β-hydroxybutyrate concentration and increased plasma lactate concentration compared with CON both before and after feeding. The PA treatment also increased hepatic pyruvate and lactate concentrations compared with CON. The PA treatment tended to increase hepatic isocitrate and fumarate concentrations but did not affect hepatic malate and oxaloacetate concentrations, suggesting that elevated mitochondrial NADH/NAD may have slowed the isocitrate dehydrogenase and fumarase reactions. The PA treatment also increased succinate concentration compared with CON, suggesting that a bottleneck may be present at succinate dehydrogenase. The PA treatment tended to increase citrate concentration despite having no effects on acetyl-CoA or oxaloacetate concentrations. These results are in agreement with our hypothesis that rapid absorption of propionate from the rumen and extraction by the liver results in metabolic bottlenecks in the liver that may affect feeding behavior and dry matter intake in dairy cows in the PP period.
本研究旨在确定奶牛产后(PP)期肝脏丙酸代谢的潜在短期代谢瓶颈,以及这些瓶颈如何受到饲养状态的影响。丙酸主要由淀粉发酵产生,会降低 PP 期奶牛的干物质摄入量,这可能是通过刺激肝脏中乙酰辅酶 A 的氧化来实现的。在这项研究中,给 8 头奶牛(2 个 4 头的组,PP 后 6.63 ± 1.19 天;体况评分为 2.84 ± 0.39)瘤胃中分别给予 1.5 mol/500 mL 丙酸(PA)或 500 mL 水(对照;CON)脉冲剂量,在 4×4 拉丁方设计中,以 2×2 的处理因子排列,在饲喂前 1 小时或饲喂后 2 小时进行处理。在给药前 -1、10 和 20 分钟,在给药前 -30、-20、-10、-1、5、10、15、20、25、30 和 60 分钟时采集肝组织样本,我们假设丙酸的快速吸收导致酶饱和和辅助因子需要再生等瓶颈。PA 处理迅速增加了血浆丙酸和胰岛素浓度,无论饲喂状态如何,5 分钟时达到峰值,并在 30 分钟内从血浆中清除。PA 处理在饲喂前 30 分钟内降低了血浆非酯化脂肪酸浓度,而饲喂后则没有。PA 处理与 CON 相比,无论是在饲喂前还是饲喂后,均降低了血浆 β-羟丁酸浓度,增加了血浆乳酸浓度。PA 处理还增加了肝丙酮酸和乳酸浓度,与 CON 相比。PA 处理增加了肝异柠檬酸和延胡索酸浓度,但对苹果酸和草酰乙酸浓度没有影响,这表明升高的线粒体 NADH/NAD 可能减缓了异柠檬酸脱氢酶和延胡索酸酶反应。PA 处理还增加了琥珀酸浓度,与 CON 相比,这表明琥珀酸脱氢酶可能存在瓶颈。尽管对乙酰辅酶 A 或草酰乙酸浓度没有影响,但 PA 处理增加了柠檬酸浓度的趋势。这些结果与我们的假设一致,即丙酸从瘤胃中的快速吸收和肝脏的提取导致肝脏中的代谢瓶颈,这可能影响 PP 期奶牛的采食行为和干物质摄入量。