NUTRIENT UTILIZATION BY INTESTINAL CELLS OF AGED ANIMALS

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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).