围产期奶牛能量负平衡引发胰岛素抵抗的分子机制

项目名称： 围产期奶牛能量负平衡引发胰岛素抵抗的分子机制

项目编号： No.31472247

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 农业科学

项目作者： 刘国文

作者单位： 吉林大学

项目金额： 88万元

中文摘要： 围产期能量负平衡奶牛存在胰岛素抵抗，而胰岛素抵抗不仅能加剧能量负平衡，还增加围产期感染性疾病的发生。基于能量负平衡导致高非酯化脂肪酸（NEFA）血症和高β羟丁酸（BHBA）血症这一事实，提出高NEFA血症和高BHBA血症有可能是引发围产期能量负平衡奶牛胰岛素抵抗的重要因素的科学假设。据此，本项目观测高NEFA和/或高BHBA对脂肪组织和肝脏胰岛素敏感性及胰岛素信号通路的影响，明确高NEFA和/或高BHBA能引发外周组织器官胰岛素抵抗和干扰胰岛素信号转导；观测高NEFA和/或高BHBA对肝细胞和脂肪细胞Toll样受体介导的炎性信号通路、内质网应激信号通路和线粒体代谢通路的影响，探寻高NEFA和/或高BHBA对脂肪细胞和肝细胞炎症、应激等能影响胰岛素信号转导有关的信号通路的作用。阐明能量负平衡奶牛高NEFA和/或高BHBA血症诱发胰岛素抵抗的信号机制，为防治奶牛能量负平衡性疾病提供理论依据。

中文关键词： 围产期奶牛；能量负平衡；胰岛素抵抗；分子机制

英文摘要： In transition period, dairy cows with negative energy balance displayed insulin resistance. Insulin resistance could increase negative energy balance and then increase the incidence of infectious diseases in dairy cows. Negative energy balance could induce high blood concentration of nonesterified fatty acid (NEFA) and/or β-hydroxybutyric acid (BHBA). Therefore, we hypothesized that high blood concentration of NEFA and BHBA might be the main pathogenic factor for the incidence of insulin resistance in dairy cows. In this study, the effects of high concentration of NEFA and/or BHBA on the sensibility of insulin signaling pathway were detected, which revealed high concentration of NEFA and/or BHBA could induce insulin resistance and impair insulin signaling pathway in peripheral tissues and organs. Furthermore, the effects of high concentration of NEFA and/or BHBA on the changes of key molecules involved in TLR-medicated inflammatory signaling pathway, endoplasmic reticulum stress signaling pathway, and mitochondrial dysfunction signaling pathway in the hepatocytes and adipocytes were determined. Therefore, the mechanism of insulin resistance induced by high concentration of NEFA and/or BHBA in dairy cows with negative energy balance could be revealed. This study will provide a valuable theoretical base to reduce the incidence of energy metabolic diseases in the transition period of dairy cows.

英文关键词： periparturient period of dairy cows;negative energy balance;insulin resistance;molecular mechanism