GI AND CARDIAC ADAPTATION TO SEMI-STARVATION AND REFEEDING

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Obesity has been cited as America's most prevalent nutrition problem and "as a potential killer." In light of overwhelming evidence, obesity has been described as a disease that has significant adverse effects on morbidity and mortality. Approximately 34 million American adults are considered obese. Drastic caloric restriction can be extremely hazardous, however, potentially serious risks associated with semi-starvation (SS) diets have not been studied in a systematic, controlled manner. Specific pathogenesis of cardiac complications associated with rapid, massive weight loss have not been satisfactorily explained. The rapid reversal of SS by refeeding (RF) frequently leads to cardiac aberrations that are not fully understood. The effects of SS and RF on the gut have been almost completely ignored, even though this organ system creates the interface between dietary nutrients and subsequent metabolism and utilization. The overall goal of this proposal is to determine the cardiac and gut response to nutritionally optimal liquid protein diet versus a nutritionally optimal but low-calorie SS liquid protein diet, and subsequent RF in a dietary obese rat model. Nitrogen economy will be determine by serial N balance, and by determination of protein, RNA, DNA concentrations of cardiac and q.i. organ (pancreas, liver, small intestine) tissues. Comparative studies will be made of selected pancreatic enzyme activity (amylase, chymotrypsin, trypsin); intestinal enzymes (maltase, sucrase, lactase); liver lipid concentration; cardiac Ca, K, P, Zn, Cu and Mg concentrations. Histology will assess the morphological characteristics of the liver, pancreas, intestine and cardiac tissue. Cardiac function will be monitored by in vivo direct recording of electrocardiogram subjected to computer analysis. In subset of animals, detailed analysis of cardiac ultrastructure by electron microscopy will be studied, and absorptive function of the duodenum and ileum will be assessed using a closed intestinal loop perfusion system.