Lipoprotein structure in male subjects during in vivo lipolysis: effect of an anti-lipolytic treatment with acipimox.
Plasma free fatty acid (FFA) levels were raised in healthy volunteers by the administration of a fatty meal and epinephrine infusion (0.15 mg/kg per min), to test the hypothesis that enhanced lipolysis might lead to changes in lipoprotein distribution and to the formation of lipoprotein complexes, also impairing the interconversion of high density lipoproteins (HDL). The study was carried out in double-blind conditions in volunteers pre-treated with either placebo or with acipimox, a nicotinic acid analogue with a long-lasting activity. Lipolysis was effectively induced; the treatment with acipimox prevented the rise of free fatty acids (FFA), and it also blunted the triglyceride (TG) increase occurring during the test. Whereas the mean low density lipoprotein (LDL) particle size did not change, the HDL particle distribution showed a progressive shift to smaller particles, both after placebo and after acipimox, the changes in size being maximal 3-7 h after the meal. Evaluation of HDL interconversion in plasma samples incubated at 37 degrees C for 6 h showed the expected accumulation of HDL2a particles, with a parallel decrease of HDL3a; however, this conversion was not affected by the presence of elevated FFA levels and no difference was noted in subjects taking either placebo or acipimox. These clinical data fail to confirm the hypothesis that enhanced lipolysis may lead to dramatic changes in plasma lipoprotein distribution and/or in aggregation or fusion of lipoprotein particles, as reported from in vitro experiments. This study, however, successfully achieved a useful model of exaggerated lipolysis and confirmed the important activity of a low dose nicotinic acid analogue in inhibiting lipolysis.
Pazzucconi
F
F
Institute of Pharmacological Sciences, University of Milano, Italy.
Franceschini
G
G
Gianfranceschi
G
G
Brambilla
E
E
Sirtori
C R
CR
D000328:Adult; D004311:Double-Blind Method; D004837:Epinephrine / Q000008:administration & dosage; D005223:Fats / Q000008:administration & dosage; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D008066:Lipolysis / Q000502:physiology*; D008074:Lipoproteins / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011719:Pyrazines / Q000494:pharmacology*
D005223:Fats; D000960:Hypolipidemic Agents; D008055:Lipids; D008074:Lipoproteins; D011719:Pyrazines; C027696:acipimox; D004837:Epinephrine