One of the most rapidly increasing human public health problems is obesity, whose sequelae like type-2 diabetes, represent continuously worsening, life-long conditions. Over the last 15 years, data have begun to emerge from human and more frequently, mouse studies, that support the idea that parasitic worm infection can protect against this condition. We have therefore investigated the potential of two synthetic small molecule analogues (SMAs) of the anti-inflammatory Acanthocheilonema viteae product ES-62, to protect against metabolic dysfunction in a C57BL/6 J mouse model of high calorie diet-induced obesity. We found weekly subcutaneous administration of the SMAs in combination (1 μg of each), starting one week before continuous exposure to high calorie diet (HCD), decreased fasting glucose levels and reversed the impaired glucose clearance observed in male mice, when measured at approximately 7 and 13 weeks after exposure to HCD. Fasting glucose levels were also-reduced in male mice fed a HCD for some 38 weeks when given SMA-treatment 13 weeks after the start of HCD, indicating an SMA-therapeutic potential. For the most part, protective effects were not observed in female mice. SMA treatment also conferred protection against each of reduced ileum villus length and liver fibrosis, but more prominently in female mice. Previous studies in mice indicate that protection against metabolic dysfunction is usually associated with polarisation of the immune system towards a type-2/anti-inflammatory direction but our attempts to correlate improved metabolic parameters with such changes were unsuccessful. Further analysis will therefore be required to define mechanism of action. Nevertheless, overall our data clearly show the potential of the drug-like SMAs as a preventative or treatment for metabolic dysregulation associated with obesity.

肥胖是人类发展最快的公共​​健康问题之一，其后遗症像2型糖尿病一样，代表着持续恶化的终身状况。在过去的15年中，数据已经开始从人类中获得，并且更频繁地从小鼠研究中获得数据，这些数据支持寄生虫蠕虫感染可以预防这种情况的观点。因此，我们研究了消炎棘皮棘皮动物蛋白的两种合成小分子类似物（SMA）的潜力产品ES-62，可防止高热量饮食诱发的肥胖的C57BL / 6 J小鼠模型中的代谢功能障碍。我们发现，在连续暴露于高热量饮食（HCD）之前一周开始，每周一次皮下注射SMAs（每种1μg），在大约30℃下进行测量时，降低了空腹血糖水平并逆转了雄性小鼠中观察到的葡萄糖清除受损。接触HCD后7和13周。在HCD开始后13周接受SMA治疗的雄性小鼠，喂食HCD约38周后，其空腹血糖水平也降低，表明SMA具有治疗潜力。在大多数情况下，在雌性小鼠中未观察到保护作用。SMA治疗还可以防止回肠绒毛长度减少和肝纤维化，但在雌性小鼠中更为明显。先前在小鼠中的研究表明，针对代谢功能障碍的保护作用通常与免疫系统朝2型/抗炎方向的极化有关，但是我们尝试将改善的代谢参数与此类变化相关联的尝试并未成功。因此，需要进一步的分析来确定作用机理。然而，总体而言，我们的数据清楚地表明，类药物SMAs可以作为预防或治疗肥胖相关代谢异常的潜力。因此，需要进一步的分析来确定作用机理。然而，总体而言，我们的数据清楚地表明，类药物SMAs可以作为预防或治疗肥胖相关代谢异常的潜力。因此，需要进一步的分析来确定作用机理。然而，总体而言，我们的数据清楚地表明，类药物SMAs可以作为预防或治疗肥胖相关代谢异常的潜力。