Regulation of human intestinal nutrient absorption by adipocyte-derived factors

肥胖是一种与身体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肥胖，而且这一比例正在变得 在世界范围内日益普遍。它在阿巴拉契亚地区特别流行，西弗吉尼亚州 拥有全美最高的肥胖率。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。肥胖症患者肠道营养物质吸收改变的机制不是很好 明白了。我们的总体假设是，在肥胖期间，脂肪细胞衍生的因子改变了营养 肠上皮细胞(IECS)和结肠癌细胞的转运蛋白功能影响营养 动态平衡。最近的研究表明，炎症信号发生在IECs和脂肪细胞之间 在没有免疫细胞的情况下进行共培养。这里提出的研究将为我们提供对 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 测定脂肪细胞衍生因子对营养物质活性和表达的影响及调节 人肠上皮细胞和结肠癌细胞中的转运蛋白。使用病人来源的肠上皮有机类物质 培养模型，我们将研究与人IECs共培养的关键营养物质的摄取 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 结肠癌细胞中的关键营养物质。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.