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。虽然在提高肉牛饲料效率方面已经投入了大量的研究，但在肉牛身上，许多影响动物变异性的潜在生物学机制还没有被很好地理解。在牛和羊中观察到了胰岛素抵抗，但肉牛的饲料效率与胰岛素抵抗的关系尚不明确。我的总体假设是，动物饲料效率的可变性在一定程度上与动物对胰岛素反应的差异有关。这项发现基金的具体目标是：1)确定[由牛的葡萄糖耐量试验(GTT)和绵羊的高胰岛素-正常血糖钳(HEC)表示的]胰岛素抵抗与肥育牛和羔羊的生长性能和饲料效率之间的关系，并确定肌肉、肝脏组织和胰腺细胞形态中与胰岛素抵抗和饲料效率(脂肪因子/炎症反应、溶解/脂肪生成、能量信号)相关的代谢标记物；2)参照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，以便在不可能进行密集采样时使用。并开发数学模型来预测饲喂早期的效率分类，以及3)确定胰岛素抵抗的改善是否会提高饲料效率。为了解决这一假设，将进行一系列动物实验。这项拟议的研究将利用体内试验(Performance Trials，GTT，HEC)和Western blotting，评估全身胰岛素敏感性指标与能量代谢相关代谢标志、脂肪分解/脂肪生成和瘦素、肝脏和肌肉组织的炎症反应以及饲料效率指标(饲料摄入量、剩余饲料摄入量和饲料转化率)之间的关系。随之而来的工作将评估各种可用模型来表明肉牛的胰岛素抵抗，并建议一种方法，在不可能进行密集采样的情况下，该方法可能有助于识别牛的胰岛素抵抗。此外，这项工作还将为一名硕士、一名博士和两名本科生提供培训。本研究将对胰岛素抵抗和饲料效率在反刍动物中的作用提供新的认识，并将从整体上加深对影响饲料效率的生物学机制的理解。

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.