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

对于高产奶牛来说，围产期代表着一种与高代谢需求相关的应激状态。由于体内脂肪的大量流动，非酯化脂肪酸(NEFA)过量流入肝脏，导致肝脏严重的代谢负担，通常导致肝功能受损，导致脂肪肝和酮病。平衡NEFA的释放和消耗可以为改善高产奶牛的代谢问题提供可能性。基于自己对肥胖大鼠、绵羊和猪进行的研究，计划中的项目旨在调查一种假设，即围产期高剂量的瘤胃保护烟酸能够导致快速抽动糖酵解纤维(II型纤维)向慢速抽动氧化纤维(I型纤维)转变。这种肌肉纤维类型的转换预计会伴随着血管形成的改善和奶牛骨骼肌中血液流量的增加。这些事件反过来可能与NEFA被骨骼肌摄取增加、血浆NEFA浓度降低、流向肝脏的NEFA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减少，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。为了验证这一假设，对30头高产奶牛进行了试验，将其分成两组，对照组和添加高剂量瘤胃保护烟酸的试验组。为了研究骨骼肌的变化，将在三种不同肌肉的活组织中确定纤维类型分布(I型纤维与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肉纤维类型转换的关键调节因素，以及参与脂肪酸摄取和氧化的基因在mRNA和蛋白质水平上的作用。为了证明补充烟酸可以减轻肝脏的负担，将测定血浆中NEFA和β-羟基丁酸的浓度、肝脏中三酰甘油的浓度以及肝脏中参与酮生成的基因的表达。

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.