EFFECT OF FAT AND FIBER ON COLONIC INTESTINAL EPITHELIAL CELLS

脂肪和纤维对结肠肠上皮细胞的影响

• 批准号: 6115866
• 负责人: STEVEN J SHIFF
• 金额: $ 4.54万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6115866
• 关键词: biopsy; blood chemistry; butyrates; clinical research; colon neoplasms; dietary fiber; dietary lipid; endoscopy; feces analysis; gastrointestinal epithelium; gene mutation; human subject; nutrition related neoplasm /cancer; nutrition related tag; oncogenes

This research examines the effect of different levels of dietary fat and fiber on the proliferation and death of colonic epithelial cells. Subjects are given a well-controlled diet (weight maintaining, metabolic), with fat/fiber combination (high, normal or low fat and high, normal or low fiber) as the independent variable. Upon admission, after baseline endoscopic biopsy (by flexible sigmoidoscopy), subjects are placed on a low fat, high fiber diet for 4 wks. Assessment of colonic epithelium, sodium butyrate, and Ki-ras oncogene mutations are performed using endoscopic biopsy, blood, and stool samples. SIGNIFICANCE OF STUDY: Colon cancer is a common human malignancy. Dietary fat and fiber have been shown to affect the incidence of colorectal cancer. Populations consuming diets high in fat and low in fiber overall have greater incidence rates of colorectal cancer, compared to populations consuming less fat and more fiber. It is not entirely clear whether dietary fat and fiber are independent variables with respect to colon carcinogenesis. Sodium butyrate, a short chain fatty acid, is generated in the colon in large quantities as dietary fiber is fermented by colonic bacteria. Sodium butyrate, in vitro, reduces the proliferation and induces apoptosis in cultured colon cancer cells.

本研究探讨了不同水平的膳食脂肪和纤维对结肠上皮细胞增殖和死亡的影响。受试者饮食控制良好（维持体重、代谢），以脂肪/纤维组合（高、正常或低脂肪，高、正常或低纤维）为自变量。入院后，在基线内镜活检（通过柔性乙状结肠镜）后，受试者接受低脂肪、高纤维饮食4周。通过内镜活检、血液和粪便样本评估结肠上皮、丁酸钠和Ki-ras癌基因突变。研究意义：结肠癌是人类常见的恶性肿瘤。膳食脂肪和纤维已被证明会影响结直肠癌的发病率。总体而言，与摄入较少脂肪和较多纤维的人群相比，摄入高脂肪和低纤维饮食的人群结直肠癌的发病率更高。目前还不完全清楚膳食脂肪和纤维在结肠癌发生中是否是独立变量。丁酸钠是一种短链脂肪酸，在结肠细菌发酵膳食纤维时，在结肠中大量产生。丁酸钠对体外培养的结肠癌细胞具有抑制增殖和诱导凋亡的作用。