NUTRIENT UTILIZATION BY INTESTINAL CELLS OF AGED ANIMALS

老年动物肠细胞的营养利用

• 批准号: 3122727
• 负责人: SHARON E FLEMING
• 金额: $ 19.57万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-06-15 至 1996-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3122727
• 关键词: age difference; bioenergetics; carbon; carbon dioxide; colon; enzyme activity; fasting; gastrointestinal system; jejunum; laboratory rat; nutrient bioavailability; nutrition related tag

Oxidative metabolism by intestinal cells, and the adaptation by these cells to short-term deprivation of energy (48 hr fast) or to longer-term deprivation of lumenal nutrients (4 wk dietary change), will be studied. Our first hypothesis is that, as in other tissues, intestinal cells of young animals will adjust to conserve essential nutrients under these conditions. Our second hypothesis is that, in intestinal cells of aged animals, this adaptive response will occur to a lesser extent. The first hypothesis is based on in vivo data of others showing that jejunal cells of young rats utilize glucose and glutamine when fed and, when fasted, they utilize ketone bodies and glutamine. As the influence of aging on oxidative metabolism of intestinal cells has not been investigated, our second hypothesis is based on data from the liver, adipose tissue and mesenteric lymph nodes suggesting that substrate utilization differs between young and aged rats. There is evidence also that the aged respond to a fasting or dietary changes differently than the young, and this has been observed in measures of cellular proliferation throughout the gut, in mucosal disaccharidases and in pancreatic enzymes. In our studies, the oxidation of substrates by both the jejunum and colon will be assessed for several reasons: both segments play important roles in health and disease; the preferred fuels may differ for these two segments, although no in vivo data are available for colon cells; and the availability of lumenal nutrients changes in response to diet and fasting in both segments. The Fischer 344 rat will be used in all studies as it has been well characterized with respect to digestion, pathology and longevity. In vivo studies will be used to calculate the fractional contribution of several nutrients to total respiration by each intestinal segment. To do this, small quantities of radioactive substrates will be infused into the artery providing blood to the segment, and venous blood from the segment will be quantitatively collected and analyzed for metabolites. In vitro studies will be used to provide information regarding the potential for oxidation of each nutrient when substrate is not limiting. Carbon dioxide production from labelled substrates will be quantified using suspensions of cells isolated from the jejunum and colon. The reliability of these in vitro techniques will be assessed by making comparisons with the in vivo data. In other studies, enzyme activities and metabolite concentrations in cells will be quantified in order to determine how oxidative metabolism in intestinal cells is controlled and how, in cells of aged animals, this control is altered. Data regarding the importance of oxidizable substrates have been used to suggest strategies for maintaining health and for preventing and recovering from intestinal disease (eg: supplementation of TPN with glutamine, and ingestion of dietary fiber as substrate for SCFA production).

肠细胞的氧化代谢和这些细胞的适应 短期能量剥夺（禁食48小时）或长期 将研究腔内营养素的剥夺（4周饮食变化）。 我们的第一个假设是，与其他组织一样， 年轻的动物将调整，以保存必要的营养素下， 条件 我们的第二个假设是，在老年人的肠细胞中， 动物，这种适应性反应将在较小程度上发生。 第一 这一假设是基于其他人的体内数据，表明 幼鼠在进食时利用葡萄糖和谷氨酰胺，在禁食时， 利用酮体和谷氨酰胺。 随着年龄的增长， 我们尚未研究肠细胞的氧化代谢， 第二个假设是基于来自肝脏、脂肪组织和 肠系膜淋巴结表明底物利用不同 年轻和年老的老鼠。 也有证据表明老年人 与年轻人不同的禁食或饮食变化， 在整个肠道的细胞增殖测量中观察到， 粘膜二磷酸腺苷酶和胰腺酶。 在我们的研究中， 将评估空肠和结肠对底物的氧化， 几个原因：这两个部分在健康和疾病方面都发挥着重要作用; 对于这两个部分，优选的燃料可以不同， 数据可用于结肠细胞;和管腔的可用性 营养素的变化，以应对饮食和禁食在这两个部分。 的 Fischer 344大鼠将用于所有研究，因为其表现良好 以消化、病理和寿命为特征。 体内 研究将被用来计算几个分数的贡献， 营养素到总呼吸量的比率。 要执行此操作， 少量的放射性物质将被注入动脉 将血液提供给该节段，并且来自该节段的静脉血将被 定量收集并分析代谢物。 体外研究 将用于提供有关氧化潜力的信息 当基质不受限制时， 二氧化碳产生 将使用细胞悬液定量标记底物的 分离自空肠和结肠。 这些体外试验的可靠性 将通过与体内数据进行比较来评估这些技术。 在其他研究中，细胞中的酶活性和代谢物浓度 将被量化，以确定如何氧化代谢， 肠细胞是如何控制的，以及在老年动物的细胞中， 控制被改变。 关于可氧化底物重要性的数据 已经被用来建议维持健康的策略， 预防和恢复肠道疾病（例如：补充 含谷氨酰胺的TPN，以及作为SCFA底物的膳食纤维摄入 生产）。