Understanding biological mechanisms influencing feed efficiency in beef cattle: insulin resistance

在牛肉生产中，饲料是主要的生产成本。 虽然大量的研究已经投入到提高肉牛饲料效率，许多潜在的生物学机制影响动物的变异性没有很好地了解肉牛。在牛和羊中观察到胰岛素抵抗，但与肉牛饲料效率的关系尚不明确。我的总体假设是，动物饲料效率的差异部分与动物胰岛素反应性的差异有关。本研究资助的具体目标是：1）表征胰岛素抵抗[通过牛的葡萄糖耐量试验（GTT）和绵羊的高胰岛素-正葡萄糖钳夹（HEC）表明]与肥育肉牛和羔羊生长性能和饲料效率指标之间的关系，并确定与胰岛素抵抗和饲料效率相关的代谢标志物肌肉和肝组织以及胰腺细胞形态中的（脂肪因子/炎症反应、脂肪分解/脂肪生成、能量信号传导），2）参考GTT评估胰岛素抵抗指数，并确定最能预测胰岛素抵抗的指数，以在不可能进行密集采样时使用，并开发数学模型以在饲喂期早期预测效率分类，以及3）确定胰岛素抗性的改善是否将改善饲料效率。为了解决这一假设，将进行一系列动物实验。拟议的研究将利用体内（性能试验，GTT，HEC）和蛋白质印迹法，以评估胰岛素敏感性的全身测量值与能量代谢，脂解/脂肪生成和瘦素，肝脏和肌肉组织中的炎症反应的相关代谢标志物之间的关系，以及饲料效率的测量值（采食量，剩余采食量和饲料转化率）。伴随的工作将评估各种可用的模型，以表明肉牛的胰岛素抵抗，并提出一种方法，可能是有用的，在密集的采样是不可能的，在阉牛的胰岛素抵抗的识别。此外，这项工作将提供一个硕士，一个博士和两个本科生的培训。本研究将为反刍动物胰岛素抵抗和饲料效率的作用提供新的认识，并将加深对影响饲料效率的生物学机制的整体理解。

In beef production, feed represents a major production cost. Although considerable research has been invested in improving feed efficiency in beef cattle, many of the underlying biological mechanisms influencing animal variability are not well understood in beef cattle. Insulin resistance has been observed in cattle and sheep, however the relationship to feed efficiency in beef cattle is uncharacterized. My overall hypothesis is that animal variability in feed efficiency is partially related to animal differences in insulin responsiveness. The specific objectives which will be addressed in this Discovery grant are to 1) To characterize relationships between insulin resistance [indicated by glucose tolerance test (GTT) in cattle and hyperinsulinaemic-euglycemic clamp (HEC) in sheep] and measures of growth performance and feed efficiency in finishing steers and lambs, and identify metabolic markers associated with insulin resistance and feed efficiency (adipokines/inflammatory response, lypolisis/lipogenesis, energy signaling) in muscle and hepatic tissue and pancreas cell morphology, 2) Evaluate indices of insulin resistance in reference to GTT and identify an index that best predicts insulin resistance for use when intensive sampling is not possible, and to develop mathematical models to predict efficiency classification early in the feeding period, and 3) To determine if improvement in insulin resistance will improve feed efficiency. To address this hypothesis a series of animal experiments will be conducted. The proposed research will utilize in vivo (performance trials, GTT, HEC) and western blotting, to evaluate relationships between whole body measures of insulin sensitivity and associated metabolic markers of energy metabolism, lipolysis/lipogenesis and leptin, inflammatory response in hepatic and muscle tissues, and measures of feed efficiency (feed intake, residual feed intake and feed conversion ratio). Accompanying work will evaluate various available models to indicate insulin resistance in beef cattle and suggest a method that may be useful for identification of insulin resistance in steers where intensive sampling is not possible. Additionally, this work will provide training for one MSc, one PhD, and two undergraduate students. This research will provide a novel understanding of the role of insulin resistance and feed efficiency in ruminants, and will deepen the understanding of biological mechanisms influencing feed efficiency as a whole.