Fenofibrate enhances CD36 mediated endocytic uptake and degradation of oxidized low density lipoprotein in adipocytes from hypercholesterolemia rabbit.
BACKGROUND
CD36 as a fatty acid transporter is predominantly expressed in adipocytes. We studied whether adipocytes could uptake and degrade OxLDL through CD36 and explored the effect of fenofibrate on OxLDL uptake in adipocytes from hypercholesterolemia rabbits.


METHODS
Subcutaneous adipose tissues were collected from normal, high-cholesterol and high-cholesterol plus fenofibrate treatment rabbits for adipocytes culture. CD36 and peroxisome proliferator-activated receptor gamma (PPARgamma) mRNA expression were evaluated by RT-PCR.


RESULTS
Cellular expression of CD36 was confirmed during differentiation of adipose cell by RT-PCR. Upon incubation at 37 degrees C, (125)I-OxLDL was endocytosed in a dose-dependent fashion and underwent lysosomal degradation by adipocytes. In binding experiments at 4 degrees C, (125)I-OxLDL exhibited specific and saturable binding to adipocytes (K(D) = 4.2 microg/mL). The endocytic uptake and degradation of (125)I-OxLDL by adipocytes were inhibited by 56 and 54% with anti-CD36 antibody. Fenofibrate treatment enhanced the (125)I-OxLDL uptake and degradation and up-regulated CD36 mRNA expression in adipocytes and suppressed PPARgamma mRNA expression in adipose tissue from hypercholesterolemia rabbits.


CONCLUSIONS
CD36 plays a novel role in adipose tissues and adipocytes possibly involve in clearance of OxLDL in blood. Fenofibrate treatment improved the OxLDL uptake and degradation in adipocytes from hypercholesterolemia 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
Jie
J
Zhang
Da-Qing
DQ
Ye
Hui-Jun
HJ
Liu
Ling
L
Li
Jie-Qi
JQ
D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D018955:CD36 Antigens / Q000502:physiology*; D002478:Cells, Cultured; D011345:Fenofibrate / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000378:metabolism*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D011817:Rabbits
D018955:CD36 Antigens; D000960:Hypolipidemic Agents; D008077:Lipoproteins, LDL; D011345:Fenofibrate