Regulation of human intestinal nutrient absorption by adipocyte-derived factors

肥胖是一种与体内脂肪过多有关的复杂疾病。肥胖在美国非常普遍 大约每三个成年人中就有一个被认为是肥胖的州，而且这一情况正在变得越来越严重 在世界范围内日益普遍。它在阿巴拉契亚地区尤其普遍，其中包括西弗吉尼亚州 美国肥胖率最高。有一些严重的健康问题与肥胖有关， 包括心血管疾病、2型糖尿病、高血压和多种癌症 包括结肠癌。肥胖症中肠道营养吸收的改变机制尚不完善 明白了。我们的总体假设是，在肥胖期间，脂肪细胞衍生的因素会改变营养 肠上皮细胞 (IEC) 和结肠癌细胞中的转运蛋白功能，影响营养 体内平衡。最近的研究表明炎症信号传导发生在 IEC 和脂肪细胞之间 当在没有免疫细胞的情况下共培养时。这里提出的研究将提供对 脂肪细胞衍生因子调节肠道营养吸收过程。我们的总体目标是 确定脂肪细胞衍生因子对营养物质活性和表达的影响和调节 人类 IEC 和结肠癌细胞中的转运蛋白。使用基于患者的肠上皮类器官 培养模型中，我们将检查与以下物质共培养的人类 IEC 对关键营养素的吸收情况： 原代人类脂肪细胞。我们还将确定脂肪细胞衍生因子对摄取的影响 结肠癌细胞的关键营养素。识别和理解潜在的分子机制 与肥胖相关的营养吸收变化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.