SIRT1介导烟酰胺调控围产期奶牛肝脏脂质代谢的分子机制

Hepatic lipid-related metabolic disorder in periparturient dairy cows is associated with metabolic diseases, like fatty liver and ketosis. Our preliminary experiment data have shown that nicotinamide supplementation in dairy cows peripartum can result in the reduced plasma levels of NEFA, TG and VLDL and regulate the plasma lipid spectrum of dairy cow postpartum, improving lipid metabolism. However, the underlying mechanism of lipid metabolism regulated by nicotinamide in periparturient dairy cows remain unclear. Therefore, it is hypothesized that nicotinamide supplementation in transition cows leads to increased SIRT1 deacetylase activity, furtherly inhibits hepatic lipogenesis and promotes fatty acid β-oxidation, and improves hepatic lipid metabolism of periparturient dairy cows. In vivo and in vitro trials will be conducted with the aim to investigate the mechanism of hepatic lipid metabolism regulated by nicotinamide using lipidomics and SIRT1 pathway analysis, which will be explored to provide theoretical ground on nutritional strategy for modulating hepatic lipid metabolism in periparturient dairy cows.

围产期奶牛肝脏脂质代谢紊乱易诱发代谢疾病，如脂肪肝和酮病。申请者前期研究显示，围产期补饲烟酰胺可降低奶牛产后血浆非酯化脂肪酸(NEFA)、甘油三酯(TG)和极低密度脂蛋白(VLDL)水平，并调控血浆脂质谱，改善奶牛脂质代谢。然而，烟酰胺调控围产期奶牛脂质代谢的分子机制尚不清楚。因此，本项目以“烟酰胺可通过提高SIRT1去乙酰化活性，从而抑制肝脂生成和促进脂肪酸氧化，改善围产期奶牛肝脏脂质代谢”为理论假设,拟通过体内、体外试验，采用脂质组学和SIRT1信号通路分子检测等技术，明确烟酰胺调控围产期奶牛肝脏脂质代谢的作用与机制，为围产期奶牛肝脏脂质代谢营养调控提供理论依据。