Cholesterol and triglyceride fatty acid synthesis in apolipoprotein E2-associated hyperlipidemia

To investigate whether increased endogenous lipogenesis contributes to elevated plasma lipid levels in individuals with apolipoprotein (apo) E2-associated hyperlipidemia (E2-HL), plasma pool cholesterol and triglyceride fatty acid syntheses were measured in subjects with E2-HL and in those with normal lipid levels. Subjects were given a priming dose of deuterium oxide (D2O) followed by maintenance doses over 48 hours. During the first 24 hours, subjects consumed prepared meals, whereas during the 24-48 hour interval, they consumed water only. Blood samples were drawn every 12 hours, and cholesterol and triglyceride fatty acid formation rates were determined from the change in deuterium enrichment. The free cholesterol fractional synthesis rate over 0-24 hours of E2-HL subjects (0.057 +/- 0.010 day-1, mean +/- SEM) was not significantly different from that of normolipidemics (0.075 +/- 0.005 day-1). Calculated cholesterol net synthesis was not different between the two groups (0.56 +/- 0.07 and 0.75 +/- 0.05 g/day, respectively). Mean free cholesterol synthesis for all subjects was higher in the fed (0-24 hour) compared with the fasted (24-48-hour) condition. Initial 12-hour triglyceride fatty acid fractional synthesis was significantly (p less than 0.01) increased in E2-HL subjects (0.143 +/- 0.012 day-1) compared with controls (0.082 +/- 0.0013 day-1). These findings suggest that in E2-HL, elevated plasma cholesterol levels are due to factors other than increased sterol synthesis, while higher de novo fatty acid synthesis contributes to the observed hypertriglyceridemia.