Effects of isotretinoin on the metabolism of triglyceride-rich lipoproteins and on the lipid profile in patients with acne

Isotretinoin treatment alters the plasma lipid levels but the mechanisms and the effects on the metabolism of triglyceride-rich lipoproteins such as chylomicrons and very-low-density lipoproteins remain unclear. We investigated the effect of isotretinoin on the plasma kinetics of emulsion models of triglyceride-rich lipoproteins and the lipid profile. Ten patients with acne were treated with 0.8 mg/kg of isotretinoin over 4 weeks for comparison with non-treated acne patients. In both groups the plasma kinetic study of a triglyceride-rich emulsion double-labeled with 14C-cholesterol oleate and 3H-triolein was performed after intravenous injection of the emulsion and radioactive counting in plasma samples collected over 60 min. Patients using isotretinoin showed decreased removal from the plasma of the 3H-triglyceride (median 0.019 min-1 TG) compared with controls (median 0.044 min−1, P=0.007), and the removal of the emulsion 14C-cholesterol oleate also tended to be decreased (treatment: 0.011 min−1; controls: 0.024 min−1, P=0.06). The values of total and LDL cholesterol and triglycerides were increased post-treatment (P<0.03). In conclusion, while increasing the fasting plasma concentration of VLDL and LDL, which are traditional risk factors for atherosclerosis, isotretinoin treatment also slows down the metabolism of triglyceride-rich lipoproteins such as chylomicrons, as tested by the emulsion model, an effect that is also increasingly recognized as atherogenic.