Atorvastatin reduces serum leptin concentration in hypercholesterolemic rabbits.
BACKGROUND
Leptin may play an important role in the development of atherosclerosis. We evaluated the effect of atorvastatin on leptin secretion in vivo and in vitro.


METHODS
Sixteen rabbits fed with high-cholesterol diet for 8 weeks were randomly divided into 2 groups: (1) high cholesterol diet for 6 weeks (n=8), and (2) the same cholesterol diet plus atorvastatin (2.5 mg/kg/day) for 6 weeks (n=8). A control group (n=5) was fed with normal diet for 14 weeks. Subcutaneous adipose was collected for RNA analysis. The direct effect of atorvastatin on leptin release was assayed in primary rabbit adipocytes. Leptin levels in serum and adipocytes culture supernatant were measured by ELISA. RT-PCR was used to evaluate leptin mRNA expressions in adipose and adipocytes.


RESULTS
Compared with control group, rabbits fed with high cholesterol diet showed higher levels of serum total cholesterol, LDL cholesterol and leptin, all of which were significantly reduced by atorvastatin treatment. Leptin mRNA expression of adipose was significant lower in rabbits treated with atorvastatin than those fed with high cholesterol diet continuously (0.81+/-0.31 vs. 1.23+/-0.36, P<0.05). Atorvastatin dose-dependently inhibited leptin secretion and mRNA expression in cultured adipocytes.


CONCLUSIONS
Atorvastatin can inhibit leptin release and mRNA expression, and reduces serum leptin level in hypercholesterolemic rabbits.
Zhao
Shui-ping
SP
Department of Cardiology, The Second Xiangya Hospital of Central South University, middle Ren-Min road No.86, Changsha, Hunan 410011, PR China. zhaosp@medmail.com.cn
Wu
Zhi-hong
ZH
D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue; D000818:Animals; D000069059:Atorvastatin; D002784:Cholesterol / Q000008:administration & dosage / Q000097:blood; D004353:Drug Evaluation, Preclinical; D006538:Heptanoic Acids / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D020738:Leptin / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects; D011817:Rabbits
D006538:Heptanoic Acids; D020738:Leptin; D011758:Pyrroles; D012333:RNA, Messenger; D002784:Cholesterol; D000069059:Atorvastatin