Regulation of human intestinal nutrient absorption by adipocyte-derived factors

肥胖症是一种与体内脂肪过多有关的复杂疾病。肥胖症在美国非常普遍， 在美国，大约每三个成年人中就有一个被认为是肥胖的， 在世界范围内越来越普遍。它在阿巴拉契亚地区尤其普遍，西弗吉尼亚州 肥胖率是美国最高的有几个严重的健康问题与肥胖有关， 包括心血管疾病、2型糖尿病、高血压和几种癌症 包括结肠癌肥胖症患者的肠道营养吸收发生改变， 明白我们的总体假设是，在肥胖过程中，脂肪细胞源性因子改变了营养成分， 肠上皮细胞（IEC）和结肠癌细胞中的转运蛋白功能， 体内平衡最近的研究表明，炎症信号发生在IEC和脂肪细胞之间 当在不存在免疫细胞的情况下共培养时。这里提出的研究将提供深入了解 脂肪细胞衍生因子对肠道营养吸收过程的调节。我们的总体目标是 确定脂肪细胞衍生因子对营养素活性和表达的影响和调节 人肠上皮细胞和结肠癌细胞中的转运蛋白。使用基于患者来源的肠上皮类器官 培养模型，我们将研究与人IEC共培养的人IEC中关键营养素的摄取， 原代人脂肪细胞我们还将确定脂肪细胞源性因子对 结肠癌细胞中的关键营养素。识别和理解潜在的分子机制 与肥胖相关的营养吸收的改变是设计未来疗法的关键。

Obesity is a complex disease related to having excess body fat. Obesity is highly prevalent in the United States, where approximately one of every three adults is considered obese, and it is becoming increasing common worldwide. It is particularly prevalent in the Appalachian region, with West Virginia having the highest obesity rate in America. There are several serious health issues linked to obesity, including cardiovascular disease, type 2 diabetes mellitus, hypertension, and several cancer types including colon cancer. Intestinal nutrient absorption is altered in obesity by mechanisms that are not well understood. Our overall hypothesis is that during obesity, adipocyte-derived factors alter nutrient transporter function in intestinal epithelial cells (IECs) and colon cancer cells, which affects nutrient homeostasis. Recent work showed that inflammatory signaling occurs between IECs and adipocytes when co-cultured in the absence of immune cells. The studies proposed here will provide insight into the regulation of intestinal nutrient absorption processes by adipocyte-derived factors. Our overall aim is to determine the effect and regulation of adipocyte-derived factors on activity and expression of nutrient transporters in human IECs and colon cancer cells. Using patient-derived intestinal epithelial organoidbased culture models, we will examine the uptake of key nutrients in human IECs co-cultured with primary human adipocytes. We will also determine the effect of adipocyte-derived factors on uptake of key nutrients in colon cancer cells. Identifying and understanding the molecular mechanisms underlying obesity-related alterations in nutrient absorption is key for designing future therapeutics.