Metabolism of glucose and fatty acid by leukocytes from patients with endogenous hypertriglyceridemia.

The metabolic abnormalities responsible for endogenous hypertriglyceridemia have not been defined. Some in vivo studies have suggested that excessive triglyceride production is the cause of this defect. In an attempt to obtain direct evidence concerning this mechanism, we have compared in vitro the metabolism of radioactive glucose and palmitate by leukocytes from patients with endogenous hypertriglyceridemia and normal subjects. Leukocytes from the patients incorporated 9.82 plus or minus 1.7 (S.E.M.) nanomoles of glucose into cellular lipid per 10-8 cells per hour. When the cell lipid extract was sugjected to mild alkaline hydrolysis, 92 per cent of the glucose radioactivity was recovered in the glycerol backbone of the lipid esters. Comparison of specific yields of CO2 from glucose labeled in the 1- or 6- position revealed that 0.53 plus or minus 0.02 per cent was metabolized via the pentose cycle. The leukocytes from hypertriglyceridemic persons incorproated 140 plus or minus 6.9 nanomoles of [1-14C]-palmitate per 10-8 cells per hour. Eighty-four per cent of the radioactivity was in triglycerides and 14 per cent in phospholipids. The major phospholipid into which palmitate was incorporated was phosphatidyl choline. The leukocytes oxidized palmitate at a rate of 2.88 plus or minus 0.23 nanomoles per 10-8 cells per hour. There were no differences in any of the above values between leukocytes from hypertriglyceridemic patients and normal subjects. Likewise, there was no correlation between the plasma triglyceride concentration and glucose or palmitate incorporation into triglycerides. To the extent that leukocytes reflect systemic metabolic processes, these data provide no support for the interpretation that the mechanism of the plasma triglyceride elevation is excessive biosynthesis.