Previous findings from this laboratory indicate that the hypertriglyceridemia associated with gram-negative sepsis is a consequence of a decrease in the rate of triglyceride clearance from the blood. Although synthesis rates of liver triglycerides, cholesterol, and phospholipids are higher during gram-negative sepsis, the secretion of triglycerides is impaired resulting in an accumulation in the liver. This study will define further the factors that may lead to changes in the clearance of very-low-density lipoprotein (VLDL) triglycerides by characterizing the plasma lipoproteins with respect to their size and apoprotein and lipid composition, determining the removal rate of the B apoproteins by the liver, and measuring the liver uptake of VLDL remnants. The mechanism for the reduced secretion of liver triglycerides will be evaluated by using primary cultured hepatocytes to measure the synthesis and secretion of the apoproteins and lipids of the isolated lipoproteins. The regulation of apoprotein synthesis will be studied by measuring the effect of glucose, fatty acids, and hormones (insulin, glucagon, and dexamethasone) on the rates of synthesis and secretion of the apoproteins and lipids. To study why triglyceride synthesis is increased in the liver during gram-negative sepsis, primary cultured hepatocytes will be used to measure the uptake of fatty acids, the concentration of glycerol 3 phosphate and malonyl coenzyme A, and the activities of phosphatidate phosphohydrolase, glycerophosphate acyltransferase and carnitine palmitoyltransferase. These proposed studies on the metabolism of the lipoproteins are necessary to further our understanding of the mechanisms involved in the development of hypertriglyceridemia during gram-negative sepsis. Information obtained from these experiments will proivide guidelines for better nutritional support.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM031828-04
Application #
3280173
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1985-07-01
Project End
1991-11-30
Budget Start
1988-08-01
Budget End
1989-11-30
Support Year
4
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Thomas Jefferson University
Department
Type
Schools of Medicine
DUNS #
061197161
City
Philadelphia
State
PA
Country
United States
Zip Code
19107