NUTRIENT UTILIZATION BY INTESTINAL CELLS OF AGED ANIMALS

肠道细胞的氧化代谢及其适应 短期的能量缺乏(48小时禁食)或长期的 剥夺管腔营养素(4周饮食改变)，将进行研究。 我们的第一个假设是，像在其他组织中一样， 幼小的动物将在这些条件下进行调整以保存必要的营养 条件。我们的第二个假设是，在老年人的肠道细胞中 动物，这种适应性反应将发生在较小的程度。第一 假说是基于其他人的体内数据显示，空肠细胞 幼鼠在喂食时利用葡萄糖和谷氨酰胺，在禁食时，它们 利用酮体和谷氨酰胺。随着年龄的增长对 肠道细胞的氧化代谢尚未得到研究，我们的 第二种假设是基于来自肝脏、脂肪组织和 肠系膜淋巴结提示底物利用不同 在幼鼠和老年鼠之间。也有证据表明，老年人会对 禁食或饮食变化与年轻人不同，这有 在整个肠道的细胞增殖指标中都观察到了 粘膜双糖酶和胰酶。在我们的研究中， 将评估空肠和结肠对底物的氧化 有几个原因：这两个部分在健康和疾病中都扮演着重要的角色； 对于这两个部分，首选的燃料可能不同，尽管在体内没有 数据可用于结肠细胞；以及管腔的可用性 在这两个部分中，营养物质都会随着饮食和禁食而发生变化。这个 Fischer 344大鼠将用于所有研究，因为它一直很好 以消化、病理和长寿为特点。活体内 研究将被用来计算以下几项的部分贡献 每个肠段的营养物质占总呼吸的比例。要做到这点， 少量的放射性底物将被注入动脉 为节段提供血液，节段的静脉血将被 对代谢物进行定量收集和分析。体外研究 将用于提供有关氧化潜力的信息 当底物不受限制时，每种养分的含量。二氧化碳生产 将使用细胞悬浮液对标记的底物进行定量 从空肠和结肠中分离出来。这些药物在体外的可靠性 这些技术将通过与体内数据进行比较来进行评估。 在其他研究中，细胞中的酶活性和代谢物浓度 将被量化，以确定氧化代谢如何 肠道细胞是如何控制的，以及在老年动物的细胞中，这是如何 控制被更改。关于可氧化底物重要性的数据 已经被用来建议保持健康和 预防和康复肠道疾病(例如：补充 谷氨酰胺全胃肠外营养，以膳食纤维为底物的SCFA 生产)。

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).