脂肪肝是奶牛分娩前后常见的代谢性群发疾病，带来巨大经济损失。该病是否受某些关键基因的控制还限于参数预测的层面。本项将阐明MEN1是否调控该病发作的关键基因。抑癌基因MEN1（编码Menin蛋白）不仅可以调控胰岛素的分泌影响肝糖异生/糖原分解；而且，肝脂变性的老龄鼠肝脏中Menin的表达降低，而过量表达Menin降低肝中甘油三酯累积，抵御脂肪肝发生。这与初始数据疑似脂肪肝大鼠Menin表达下降有异曲同工之妙；同时奶牛肝脏中存在MEN1/ Menin的表达。该项借助于Men1在小鼠肝细胞中的功能，进而从胰岛素抵抗、脂肪代谢转运、氧化炎症反应、糖异生等多角度系统了解、验证MEN1基因在牛肝细胞代谢中的具体调节功能，结合MEN1在脂肪肝组织中的调控作用，综合解析MEN1在脂肪肝发病中的功能和分子调控机理。该项将为全方位理解脂肪肝的发病机理开辟新的思路，扭转目前侧重关注脂肪代谢失调研究脂肪肝的片面性

Bovine fatty liver syndrome is a type of metabolic disease, usually occurring in populations of high-yield cows before or after parturition. Estimations of quantitative genetics parameters showed occurrences of the syndrome would be associated with hereditary factors. However, no such factors were reported yet. The program will be able to answer the scientific question whether MEN1 is the central regulator in the pathogenesis of bovine fatty liver syndrome. The tumor suppressor MEN1 gene, encoding protein of Menin, is a critical gene affecting normal metabolism in the body. More importantly, the expression of Menin was found reduced in livers of aging mice, which progressed with liver steatosis. Overexpression of Menin in liver can reduce the accumulation of triglyceride (TG), decreasing the occurrence of fatty liver syndrome. The investigation will explore if the MEN1 gene is a key genetic factor that regulate normal liver metabolism or activity, and clarify its molecular regulatory roles in fatty liver syndrome. The proposal will establish its constructive views based on study of mouse Men1 gene on normal liver cells, so as to fully understand the regulatory roles of Men1 in liver activity from all-round views, such as insulin resistance, dysregulation of lipoprotein metabolism and transport, decreased mitochondrial oxidative stress and inflammation reaction, and especially gluconeogenesis. Therefore, the main dysregulated factors in each process will be screened out, allowing us to further confirm and clarify their detail genetic roles and molecular functions in maintaining normal liver activities in bovine primary hepatocytes. Meanwhile, the regulatory roles of the gene in suspect bovine liver tissues will be searched too, allowing us to reveal molecular functions of Men1 in pathogenesis of bovine fatty liver syndrome and/or bovine ketosis. The program can open up new views to understand fatty liver syndrome, altering the situation emphasizing only on lipoprotein metabolism dysregulation.