Investigations of the use of rumen-protected niacin for modulating muscle fiber type composition and improvement of oxidative metabolism in skeletal muscle of high-yielding dairy cows during the periparturient phase

对于高产奶牛，围产期代表与高代谢需求相关的应激状态。由于体内脂肪的大量动员，非酯化脂肪酸（NEFA）向肝脏的过量流动导致肝脏的严重代谢负担，通常导致肝功能受损，从而导致脂肪肝和酮症。平衡NEFA的释放和消耗可以提供改善高产奶牛中存在的代谢问题的可能性。根据自己对肥胖大鼠，绵羊和猪进行的研究，计划中的项目旨在研究以下假设，即围产期期间高剂量的瘤胃保护烟酸能够引起从快速收缩糖酵解纤维（II型纤维）到缓慢收缩氧化纤维（I型纤维）的转变。这种肌纤维类型的转换预计将伴随着改善的血管化和增加通过奶牛骨骼肌的血流量。这些事件反过来可能与骨骼肌对NEFA的摄取增加、NEFA血浆浓度降低、NEFA流向肝脏的流量减少以及NEFA对肝脏的负荷减少有关。这些变化可能导致肝脏中三酰甘油含量降低和酮体形成减少，这反过来可能有利于奶牛的肝功能和整体健康。为了研究这一假设，计划用30头高产奶牛进行实验，将其分为两组，对照组和补充高剂量瘤胃保护烟酸的组。为了研究骨骼肌的变化，将在三种不同肌肉的活检中确定纤维类型分布（I型与II型纤维）和血管形成。为了评估脂肪酸利用的能力，将考虑肌肉表型和肌纤维类型转换的关键调节因子，此外，还将考虑在mRNA和蛋白质水平上参与脂肪酸摄取和β-氧化的基因。将测定血浆中NEFA和β-羟基丁酸的浓度、三酰甘油的肝脏浓度和肝脏中参与酮生成的基因的表达，以证明补充烟酸可降低肝脏负担。

For high yielding dairy cows, the periparturient phase represents a stressful condition which is associated with a high metabolic demand. The excess flow of non-esterified fatty acids (NEFA) to the liver due to intensive mobilisation of body fat leads to a severe metabolic burden of the liver and commonly to an impairment of liver function resulting in fatty liver and ketosis. Balancing the release and the consumption of NEFA could offer possibilities to improve the metabolic problems present in high yielding dairy cows. Based on own studies performed with obese rats, sheep and pigs, the planned project aims to investigate the hypothesis that high doses of rumen-protected niacin during the periparturient phase are able to cause a shift from fast twitch glycolytic fibers (type II fibers) to slow twitch oxidative fibers (type I fibers). This muscle fiber type switching is expected to be accompanied by an improved vascularisation and an increased blood flow through the skeletal muscle of dairy cows. These events in turn might be associated with an increased uptake of NEFA into the skeletal muscle, reduced plasma concentrations of NEFA, a reduced flow of NEFA to the liver and a diminished load of the liver with NEFA. These changes might lead to a reduced triacylglycerol content in the liver and a reduced formation of ketone bodies which in turn might be beneficial for liver function and overall health of dairy cows. In order to investigate this hypothesis, an experiment with 30 high yielding dairy cows is planned which are allotted to two groups, a control group and a group supplemented with a high dose of rumen-protected niacin. In order to investigate alterations in the skeletal muscle, the fiber type distribution (type I vs. type II fibers) and the vascularisation will be determined in biopsies of three different muscles. To assess the capacity of fatty acid utilisation, key regulators of muscle phenotype and muscle fiber type switching, and besides, genes involved in fatty acid uptake and ß-oxidation on mRNA and protein levels will be considered. Concentrations of NEFA and ß-hydroxy butyric acid in plasma, liver concentrations of triacylglycerols and the expression of genes involved in ketogenesis in the liver will be determined in order to prove the reduction of the burden of the liver by supplementation of niacin.