Hepatic dysfunction frequently develops in severely malnourished patients receiving total parenteral nutrition (TPN) and may limit caloric delivery delaying nutritional repletion. Since hepatic dysfunction may reflect hepatic steatosis due to glucose delivery in excess of oxidative capacity, partial provision of calories as fat may permit increased caloric delivery without hepatic dysfunction. This hypothesis was evaluated using a protein-depleted rat-TPN model. After 4 weeks of protein depletion, rats were nutritionally repleted using one of four isonitrogenous, isovolemic intravenous diets of varying caloric content and/or composition. After 6 days of nutritional repletion massive hepatomegaly and fatty deposition were noted in animals repleted with regimens supplying all nonnitrogenous calories as fat or as carbohydrate (CHO). Hepatic steatosis was avoided when a "balanced" regimen (75% CHO; 25% fat) or a hypocaloric regimen (total calories decreased by 25%) were used, but hypocaloric TPN produced suboptimal nutritional repletion (serum albumin, transferrin, nitrogen balance, weight gain). All intravenous diets were similar to oral rat chow in their ability to restore liver nitrogen and maintain liver protein synthesis. The use of TPN regimens of "balanced" caloric composition similar to that of oral feedings (75% CHO; 25% fat) may provide a clinical alternative to hypocaloric TPN permitting optimal caloric provision and nutritional repletion without hepatic dysfunction.
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