Advanced glycation end products-modified proteins and oxidized LDL mediate down-regulation of leptin in mouse adipocytes via CD36.
Advanced glycation end products (AGE)-modified proteins as well as oxidized-LDL (Ox-LDL) undergo receptor-mediated endocytosis by CHO cells overexpressing CD36, a member of class B scavenger receptor family. The purpose of the present study was to examine the effects of glycolaldehyde-modified BSA (GA-BSA) as an AGE-ligand and Ox-LDL on leptin expression in adipocytes. GA-BSA decreased leptin expression at both protein and mRNA levels in 3T3-L1 adipocytes and mouse epididymal adipocytes. Ox-LDL showed a similar inhibitory effect on leptin expression in 3T3-L1 adipocytes, which effect was protected by N-acetylcysteine, a reactive oxygen species (ROS) inhibitor. Binding of (125)I-GA-BSA or (125)I-Ox-LDL to 3T3-L1 adipocytes and subsequent endocytic degradation were inhibited by a neutralizing anti-CD36 antibody. Furthermore, this antibody also suppressed Ox-LDL-induced leptin down-regulation. These results clarify that the interaction of GA-BSA and Ox-LDL with CD36 leads to down-regulation of leptin expression via ROS system(s) in 3T3-L1 adipocytes, suggesting that a potential link of AGE- and/or Ox-LDL-induced leptin down-regulation might be linked to insulin-sensitivity in metabolic syndrome.
Unno
Yuka
Y
Department of Medical Biochemistry, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
Sakai
Masakazu
M
Sakamoto
Yu-Ichiro
Y
Kuniyasu
Akihiko
A
Nakayama
Hitoshi
H
Nagai
Ryoji
R
Horiuchi
Seikoh
S
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism*; D002417:Cattle; D015536:Down-Regulation; D004705:Endocytosis / Q000502:physiology; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D007457:Iodine Radioisotopes / Q000378:metabolism; D020738:Leptin / Q000235:genetics / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D051379:Mice; D017382:Reactive Oxygen Species / Q000378:metabolism; D054411:Receptors, Leptin; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000378:metabolism
D018955:CD36 Antigens; D017127:Glycation End Products, Advanced; D007457:Iodine Radioisotopes; C515448:LEPR protein, human; D020738:Leptin; D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; D054411:Receptors, Leptin; C515447:leptin receptor, mouse; C099252:oxidized low density lipoprotein; D012710:Serum Albumin, Bovine