Effects of atorvastatin on lipid metabolism in normolipidemic and hereditary hyperlipidemic, non-laying hens.
As a result of a hereditable point mutation in the oocyte very low density lipoprotein (VLDL) receptor, sexually mature restricted ovulator (RO) female chickens (Gallus gallus), first described as a non-laying strain, exhibit endogenous hyperlipidemia and develop atherosclerotic lesions. In a 20-day study, RO hens and their normolipidemic (NL) siblings were fed either a control diet, or the control diet supplemented with 0.06% atorvastatin (AT), a potent 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR) inhibitor. Compared to NL hens, RO birds exhibited greatly elevated baseline plasma total cholesterol (CHOL) and triglyceride (TG) concentrations (1.56 vs. 4.55 g/l and 30.7 vs. 138.4 g/l, respectively). AT attenuated plasma CHOL and TG concentrations by 60.3% and 70.1%, respectively, in NL hens and by 45.1% and 34.3%, respectively, in RO hens. Messenger RNA levels of several key genes involved in hepatic VLDL assembly were suppressed in RO vs. NL hens, but were unaffected by AT. In contrast, AT elevated liver HMGR mRNA levels in NL and RO birds, but only NL hens exhibited an AT-associated increase in hepatic HMGR immunoreactive protein levels. Down-regulation of HMGR gene expression due to higher baseline levels of circulating CHOL may explain why RO birds responded less robustly than NL hens to AT administration.
Elkin
Robert G
RG
Department of Animal Sciences, Purdue University, West Lafayette, IN 47907-1151, USA. relkin@psu.edu
Zhong
Yuan
Y
Donkin
Shawn S
SS
Hengstschläger-Ottnad
Elke
E
Schneider
Wolfgang J
WJ
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D000069059:Atorvastatin; D001835:Body Weight; D002645:Chickens; D002784:Cholesterol / Q000097:blood; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D006538:Heptanoic Acids / Q000494:pharmacology*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006949:Hyperlipidemias / Q000235:genetics*; D050356:Lipid Metabolism / Q000187:drug effects* / Q000235:genetics; D008099:Liver / Q000033:anatomy & histology / Q000201:enzymology; D009929:Organ Size; D017354:Point Mutation; D011758:Pyrroles / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D012333:RNA, Messenger; D011973:Receptors, LDL; D014280:Triglycerides; C036053:VLDL receptor; D002784:Cholesterol; D000069059:Atorvastatin; D006903:Hydroxymethylglutaryl CoA Reductases