脂肪和肥胖相关基因、瘦素与阿勒泰大尾羊脂肪沉积的联系及调控机制研究

Altay sheep is an indigenous sheep breed in Xin Jiang. Meat quality of Altay sheep is very delicious. However, their tail fat tissue is too big, even more than 17% of body weight. How to reduce tail fat weight and does not affect intramuscular fat content，which hat has been a key problem of economic trait improvement of sheep in Xin Jiang. Fat mass and obesity associated gene (FTO) is the first gene related common obesity, and is related fatty deposition and metabolism. Evidence to date suggests that the association between SNPs in FTO and BMI is predominantly driven by increased energy intake. Subjects homozygous for the obesity-risk A allele of rs9939609 exhibit overall increased adlibitum food-intake, particularly fat consumption, and impaired satiety. FTO play a key role in regulating energy homeostasis. FTO is highly expressed in brain regions controlling feeding and energy expenditure, such as the hypothalamus. Hypothalamic FTO expression is modulated by fasting and restricted access to food, although both up-regulation and down-regulation have been reported, apparently depending on the severity of caloric restriction. Exposure to a high-fat diet also modulates hypothalamic FTO expression, with down-regulation reported with short-term exposure and up-regulation with more prolonged exposure. FTO gene mRNA expression was significantly different between skeletal muscle and fat tissues. Leptin is a peptide hormone expressed, synthesized and secreted by adipose tissue in proportion to its mass. This hormone circulates in blood and acts on the hypothalamus to regulate food intake and energy expenditure. When fat mass falls, plasma leptin levels fall stimulating appetite and suppressing energy expenditure until fat mass is restored. At present, the space-time of FTO gene expression have not been adequately addressed in sheep, and furthermore, little is known about correlation between FTO gene,leptin, and fatty deposition of the sheep. In the present study, we used Altay sheep as model to delineate a link of FTO gene,leptin,and fatty deposition by fasting and high-fat diet. FTO expression and leptin in different old and body weight sheep will be measured by RT-PCR and Western blot. Hormone levels, such as growth hormone and insulin, in serum will be measured.

新疆肉用绵羊多为脂臀型品种，虽肉用性能良好，但尾脂过大，有些品种的尾脂甚至占体重的17%以上。如何降低尾脂而又不影响肌内脂肪含量，一直是困扰新疆绵羊优良肉质性状种质资源利用的关键问题，而解决的关键是深入了解其各部位脂肪沉积的规律及其关键调节因子对脂肪调控的机制。FTO是第一个与普通肥胖相关的基因，与脂肪沉积相关，在能量平衡和脂肪代谢中起有重要作用，摄食可导致FTO表达改变。Leptin由脂肪组织分泌，可调节摄食，分解脂肪。目前，FTO、leptin和脂肪沉积间的联系并不清楚。因此，本课题选用生长快系和慢系阿勒泰大尾羊通过限饲和高脂饮食试验，采用组织学和分子生物学等技术，比较同日龄生长快系与慢系，正常、限饲与高脂饮食组绵羊FTO表达及脂肪沉积的差异，及FTO、leptin与脂肪代谢相关激素和基因表达水平间的相关性，阐明FTO、leptin与脂肪沉积之间的联系，探讨FTO调控脂肪沉积分子机制。

新疆肉用绵羊多为脂臀型品种，虽肉用性能良好，但尾脂过大，有些品种的尾脂甚至占体重的17%以上。如何降低尾脂而又不影响肌内脂肪含量，一直是困扰新疆绵羊优良肉质性状种质资源利用的关键问题，而解决的关键是深入了解其各部位脂肪沉积的规律及其关键调节因子对脂肪调控的机制。本课题研究了阿勒泰大尾羊尾脂、肾周脂脂肪细胞超显微结构；不同饲喂条件对小鼠脂肪组织中FTO、Leptin基因的影响；Leptin拮抗剂对3T3-L1脂肪细胞FTO表达的影响；正常、限饲与高脂饮食对同日龄生长高体重与低体重组绵羊FTO、leptin表达及脂肪沉积的差异，以及FTO、leptin与脂肪代谢相关激素和基因表达水平间的相关性。结果显示：阿勒泰大尾羊尾脂脂肪细胞膜的外侧有特殊的“发丝状”结构，尾脂脂肪细胞与肾周脂脂肪细胞超微结构存在明显差异。小鼠实验显示，高脂饲喂时，FTO基因的表达与体重及脂肪量成负相关，Leptin基因的表达成正相关；限饲下调了FTO和Leptin的表达，FTO和Leptin基因表达与体重及脂肪量成正相关。细胞实验显示，Leptin拮抗剂阻断Leptin与其受体结合后，导致脂肪含量下降，同时下调了FTO 的表达。阿勒泰大尾羊实验显示，正常饲喂状态下，FTO基因和蛋白的表达量与体重及脂肪量呈负相关，Leptin的表达量成正相关。正常、限饲与高脂饮食时，体重与脂肪量发生变化时，FTO基因和蛋白的表达变化与其呈负相关，而Leptin表达变化与其呈正相关。研究结果表明：阿勒泰大尾羊脂肪细胞超微结构特殊，细胞、小鼠和羊的试验表明FTO与脂肪沉积呈负相关，leptin与脂肪沉积呈正相关，Leptin在体脂沉积过程中可能具有下调FTO表达的作用。