Data_Sheet_1_In vivo Protein Interference: Oral Administration of Recombinant Yeast-Mediated Partial Leptin Reduction for Obesity Control.PDF

Obesity-related diseases are always the major health problems that concern the whole world. Serial studies have reported that obesity development is closely related to the out-of-control leptin encoded by the obesity gene (ob). The latest report declaimed “Less Is More,” a model explaining that partial leptin reduction triggers leptin sensitization and contributes to obesity control. Here, we came up with a novel concept, in vivo protein interference (iPRTi), an interesting protein knock-down strategy for in vivo partial leptin reduction. First, the specific immune response against leptin induced by the oral administration of ob recombinant yeast was confirmed. Subsequentally, leptin resistance was observed in diet-induced obese mice, and oral administration with ob recombinant yeast declined the circulating leptin and reduced significantly the body weight gain. To further investigate whether the iPRTi strategy is capable of obesity management, the diet-induced obese mice were administrated with ob recombinant yeast. All the indexes examined including the circulating leptin, triglyceride, and total cholesterol, as well as food intake and weight gain, demonstrated a positive effect of the iPRTi strategy on obesity control. In short, this study provides a novel strategy for the potential application of recombinant yeast for the therapy of obese individuals with leptin resistance.

肥胖相关疾病始终是全球关注的重大健康问题。连续的研究报告指出，肥胖的发展与肥胖基因（ob）编码的失控瘦素密切相关。最新的报告宣扬“少即是多”的理念，该模型阐释了部分瘦素减少可引发瘦素敏感化，并有助于肥胖控制。在此，我们提出了一个新颖的概念，即体内蛋白干扰（iPRTi），这是一种有趣的体内部分瘦素减少的蛋白敲低策略。首先，通过口服给予ob重组酵母诱导的针对瘦素的特异性免疫反应得到了证实。随后，观察到在饮食诱导的肥胖小鼠中存在瘦素抵抗现象，而口服给予ob重组酵母则降低了循环中的瘦素水平，并显著减少了体重增加。为进一步探究iPRTi策略是否能够进行肥胖管理，对饮食诱导的肥胖小鼠进行了ob重组酵母的给药。所检查的所有指标，包括循环瘦素、甘油三酯和总胆固醇，以及食物摄入量和体重增加，均显示出iPRTi策略在肥胖控制方面的积极效果。简而言之，本研究为重组酵母在治疗对瘦素抵抗的肥胖个体中的潜在应用提供了一种新颖的策略。