The response to injury is associated with a number of metabolic alterations. This includes hypermetabolism, hyperglycemia, and catabolism. Recent data also suggests that substrate cycling particularly lipid cycling is an important component of this response. In this research we shall determine the relationship of re-esterification to gram negative sepsis. We shall test the hypothesis that in early sepsis re-esterification is decreased but in the flow phase of the response to sepsis the re- esterification rate is increased. As a corollary to this we shall test the hypothesis that in patients with uncontrolled sepsis re-esterification rates decrease and are thus an early indication of the metabolic deterioration. We shall use these studies to determine the effectiveness of an in vitro assay of re-esterification to determine the re- esterification in vivo. We shall examine the role of the cytokines to support the process of re-esterification, and thus test the hypothesis that the cytokines are important in maintaining the substrate cycling during gram negative sepsis. This research will also study toe role of the immunoglobulins to stimulate adipocyte re-esterification. This would help to determine the observation that the Fc fragment of the immunoglobulins stimulates lipogenesis. This research will also study the effect of exogenous substrate support and body fat on the repletion of the body cell mass and on the resting energy expenditure. We shall test the hypothesis that high dextrose and branch chain amino acid TPN stimulate de novo lipogenesis. This activated system of lipid synthesis, not active in normal nutritional and metabolic states, will increase body fat. We believe that this increase in body fat increases re-esterification; and, that both de novo lipogenesis and increased re-esterification are responsible for the increased REE when critically ill patients are provided dextrose or branch chain TPN. This use of the exogenous calories to support these processes would explain the increased body fat and decreased BCM repletion in these patients. Finally we shall study the effect of the acytelation stimulating protein on re- esterification. We propose that this newly described protein stimulates re-esterification, and that it is one of the factors responsible for supporting re-esterification in the septic patient. We believe that this data will be important in determining the role of body fat and the processes of re-esterification and de novo lipogenesis in critically ill patients. The research will verify an in-vitro model of substrate cycling which can be used for further research. The results from this research will be important in improving the metabolic and exogenous nutritional TPN support of the critically ill patient particularly in terms of specific nutrients.
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