Effects of atorvastatin on fasting and postprandial complement component 3 response in familial combined hyperlipidemia.
VLDL overproduction by enhanced hepatic FFA flux is a major characteristic of familial combined hyperlipidemia (FCHL). The postprandial complement component 3 (C3) response has been associated with impaired postprandial FFA metabolism in FCHL. We investigated the effects of 16 weeks of treatment with atorvastatin on postprandial C3 and lipid changes in 12 FCHL patients. Atorvastatin significantly lowered fasting plasma C3 and triglyceride (TG) in FCHL. Fasting TG and insulin sensitivity were the best predictors of fasting and postprandial C3. Postprandial triglyceridemia and C3 response, estimated as area under the curve (AUC), were significantly lowered by atorvastatin by 19% and 12%, respectively, albeit still elevated, compared with 10 matched controls. Postprandial FFA-AUC and postheparin plasma lipolytic activities remained unchanged after atorvastatin, suggesting no major effect on lipolysis. After atorvastatin, postprandial hydroxybutyric acid-AUC, which was elevated in untreated FCHL patients, was decreased, reaching values similar to those in controls. The present data show reduction of postprandial hepatic FFA flux in FCHL by atorvastatin, providing an additional mechanistic explanation for the reduction of VLDL secretion reported previously for atorvastatin. This was accompanied by a decrease in fasting plasma C3 concentrations and a blunted postprandial C3 response to an acute oral fat load.
Verseyden
C
C
Department of Vascular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
Meijssen
S
S
van Dijk
H
H
Jansen
H
H
Castro Cabezas
M
M
D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001055:Apolipoproteins B / Q000097:blood; D000069059:Atorvastatin; D002914:Chylomicrons / Q000097:blood; D003176:Complement C3 / Q000032:analysis*; D005215:Fasting / Q000097:blood*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000097:blood* / Q000378:metabolism; D008297:Male; D019518:Postprandial Period / Q000187:drug effects* / Q000502:physiology*; D011758:Pyrroles / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D001055:Apolipoproteins B; D002914:Chylomicrons; D003176:Complement C3; D005230:Fatty Acids, Nonesterified; D006538:Heptanoic Acids; D011758:Pyrroles; D014280:Triglycerides; D000069059:Atorvastatin