The objectives are to test the hypothesis that the acute response to trauma can be separated into two components. One component involves the shifting of body fuel metabolism from glucose to lipid. The other component is a hypermetabolic response which includes increased lymphocytic activity, acute phase protein synthesis and various wound repair related processes, the sum of which result in an increased whole body protein synthesis rate (PSR). If the adaptation to lipids is effected pre-trauma only the hypermetabolic response should occur. Preliminary data from rats support the hypothesis. Pre-adaption to lipid results in less N excretion and a higher whole body protein synthesis rates post- trauma than in rats not pre-adapted to lipid. The hypothesis will be tested in rats and man. I Rats. Rats (220-240g) will be fed IG or IV one of two isonitrogenous (1.5 gN/kg/d), isocaloric (240 kcal/kg/d) diets differing in the glucose:lipid ratio. Diet G (glucose) 90:10, diet L (lipid) 20:80. We will: 1, Determine whether the reason for the whole body PSR being higher post-trauma in lipid-adapted rats is that (i) muscle protein synthesis (measured by pool flooding with 14C leucine and immunoprecipitation) are higher in the lipid- adapted group. 2, If differences are found determine whether they are related to glutamine production (by 5-13C-L glutamine). 3, Determine whether the mechanism for shift in fuel utilization following trauma is similar to that in early starvation. II Man. Patients (20) with inflammatory bowel disease on TPN requiring an exploratory laparotomy will be randomized into two groups, G and L. They will be given TPN with either glucose (group G) or 50% lipid and 50% glucose (group L) for 5 days before and 5 days after surgery. 3 days pre and 1-2 days post-op we will measure: PSR (15N glycine), glucose production (6,6 D glucose), Urea production (18O urea) and glutamine production (5-13C L- Glutamine). Daily N balance and 3 Methyl histidine (3-MeH) excretion will be measure. If the hypothesis is correct, the post- trauma N loss, 3-MeH excretion, glucose production, glutamine production should be less and the PSR greater for the L as compared to the G group.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK035612-06
Application #
3233902
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1984-07-01
Project End
1991-12-31
Budget Start
1989-01-01
Budget End
1989-12-31
Support Year
6
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Medicine & Dentistry of NJ
Department
Type
Schools of Osteopathy
DUNS #
City
Stratford
State
NJ
Country
United States
Zip Code
08084
Assimon, S A; Stein, T P (1994) Digestible fiber (gum arabic), nitrogen excretion and urea recycling in rats. Nutrition 10:544-50
Stein, T P; Yoshida, S; Schluter, M D et al. (1994) Comparison of intravenous nutrients on gut mucosal proteins synthesis. JPEN J Parenter Enteral Nutr 18:447-52
Chatzidakis, C; Lazarus, D D; Stein, T P (1994) Substrate cycling in lean and obese Zucker rats. Int J Obes Relat Metab Disord 18:287-93
Drews, D; Schluter, M D; Stein, T P (1993) Glycerol kinetics with parenteral lipid emulsions (long-chain triglycerides, medium-chain triglycerides, and structured lipids) in rats. Metabolism 42:743-8
Drews, D; Stein, T P (1992) Effect of bolus fluid intake on energy expenditure values as determined by the doubly labeled water method. J Appl Physiol 72:82-6
Yoshida, S; Leskiw, M J; Schluter, M D et al. (1992) Effect of total parenteral nutrition, systemic sepsis, and glutamine on gut mucosa in rats. Am J Physiol 263:E368-73
Rock, C S; Coyle, S M; Keogh, C V et al. (1992) Influence of hypercortisolemia on the acute-phase protein response to endotoxin in humans. Surgery 112:467-74
Drews, D; Stein, T P (1992) Effect of excess xylitol on nitrogen and glucose metabolism in parenterally fed rats. JPEN J Parenter Enteral Nutr 16:521-4
Leon, P; Redmond, H P; Stein, T P et al. (1991) Harry M. Vars Research Award. Arginine supplementation improves histone and acute-phase protein synthesis during gram-negative sepsis in the rat. JPEN J Parenter Enteral Nutr 15:503-8
Stein, T P; Rumpler, W V; Leskiw, M J et al. (1991) Effect of reduced dietary intake on energy expenditure, protein turnover, and glucose cycling in man. Metabolism 40:478-83

Showing the most recent 10 out of 20 publications