Our long-term objective in this work is to achieve an understanding of food intake control mechanisms sufficient for deriving successful therapeutic solutions to an under-estimated problem in postoperative surgical care, i.e., those patients who needed and received total parenteral nutrition (TPN) for nutritional support while off oral intake during their complex postoperative period and who, while still being nutritionally maintained on TPN, are physiologically able to eat but fail to do so adequately. We have developed a relevant and reproducible rat TPN model and an automated device for continuously detecting and recording feeding behavior. Using this model, we have studied blood, liver, and brain intermediary metabolites, amino acids, and putative neurotransmitters and correlated results with changes in feeding behavior induced by TPN infusion. In many parameters, we have found TPN-induced changes to be similar to changes from stimulation of the ventromedial (VMA) and/or lateral (LHA) hypothalamic nuclei. We have also found that selective hepatic vagotomy alters feeding behavior response to TPN infusions. While it is clear that the effector control of food intake, eating activity, is via the motor cortex, the afferent sensory pathways which signal the cortex are not well delineated. Our current hypotheses are: 1) the VMA and LHA are involved in food intake regulation as integrating centers, not as sensors of altered nutrient intake; and 2) hepatic sensors of altered nutrient intake send their signals centrally via the autonomic visceral afferent and the sympathetic nervous systems, as well as via the vagus. In this work, by intrahypothalamic microdialysis, we will repetitively measure biogenic amines, intramediary metabolites, acetylcholine and amino acid-derived neurotransmitters in the VMA and the LHA as affected by TPN infusion. These data will be correlated with feeding behavior and blood, liver and whole brain levels of these same substances, as affected by TPN infusion, in concomitantly studied animals. We will also determine the effects of total hepatic denervation upon TPN-induced alterations in feeding behavior and in blood, liver and whole brain levels of biogenic amines, intermediary metabolites, acetylcholine and amino acid- derived neurotransmitters. An improved understanding of food intake control mechanisms will provide the most likely means for solving this surgical care problem, one which now adds millions of dollars annually to national health care costs.
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