Experimental model of postprandial hypertriglyceridemia in sucrose-fed rats and the effectiveness of atorvastatin in the model.
Although postprandial hypertriglyceridemia has drawn attention as an independent risk factor of cardiovascular disease, there is no established animal model that shows a physiological transitory change in lipoprotein metabolism after ingestion of a fatty meal. We developed an animal model of postprandial hypertriglyceridemia using sucrose-fed rats, and used this model to evaluate the effect of atorvastatin on this condition. Compared with normal rats, sucrose-fed rats orally loaded with olive oil showed a high and prolonged increase in plasma triglyceride (TG) concentration accompanied by both an increase in TG secretion and decrease in TG clearance. Atorvastatin (30 mg/kg orally) for 2 weeks reduced not only fasting plasma TG concentration, but also the postprandial TG concentration. Atorvastatin also suppressed rates of TG secretion in both chylomicron (CM)-rich (d < 0.96 g/mL) and very-low-density lipoprotein (VLDL) (d = 0.96 to 1.006 g/mL) fractions after oral fat loading. Further, atorvastatin improved the elimination time of exogenous TG emulsion only in the nonfasted, namely, high plasma TG condition. These results indicate that this animal model satisfactorily replicates the postprandial hypertriglyceridemia observed in humans and may therefore be useful in evaluation of lipid-lowering agents. Furthermore, atorvastatin not only improves fasting but also postprandial lipoprotein metabolism, presumably by reducing TG secretion from the liver or intestine or both, and by secondarily increasing TG-rich lipoprotein clearance by eliminating saturation.
Funatsu
Toshiyuki
T
Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co, Ibaraki, Japan.
Kakuta
Hirotoshi
H
Takasu
Toshiyuki
T
Noguchi
Masahiro
M
Suzuki
Masanori
M
Miyata
Keiji
K
D000818:Animals; D019540:Area Under Curve; D000069059:Atorvastatin; D004041:Dietary Fats / Q000494:pharmacology; D004655:Emulsions; D006538:Heptanoic Acids / Q000627:therapeutic use*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D015228:Hypertriglyceridemia / Q000139:chemically induced* / Q000188:drug therapy*; D008074:Lipoproteins / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D000069463:Olive Oil; D010938:Plant Oils / Q000494:pharmacology; D019518:Postprandial Period / Q000502:physiology*; D011758:Pyrroles / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013395:Sucrose; D014280:Triglycerides / Q000493:pharmacokinetics / Q000494:pharmacology
D004041:Dietary Fats; D004655:Emulsions; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008074:Lipoproteins; D008079:Lipoproteins, VLDL; D000069463:Olive Oil; D010938:Plant Oils; D011758:Pyrroles; D014280:Triglycerides; D013395:Sucrose; D000069059:Atorvastatin