Glycolaldehyde-modified bovine serum albumin downregulates leptin expression in mouse adipocytes via a CD36-mediated pathway.
Previous observations by us have clarified that proteins modified by advanced glycation end products (AGEs) are recognized as effective ligands by CD36-overexpressed CHO cells and undergo receptor-mediated endocytosis. CD36, a member of the class B scavenger receptor family, also acts as a fatty acid transporter in adipocytes. Oxidized low-density lipoprotein (Ox-LDL), a ligand for CD36, is known to upregulate CD36 by activating peroxisome proliferator-activated receptor gamma (PPAR-gamma) in macrophages, whereas PPAR-gamma ligands such as troglitazone and 15-deoxy-delta12,14-prostaglandin J2 decrease leptin secretion from adipocytes. The purpose of this study was to examine effects of AGE ligands on leptin expression in adipocytes. Glycolaldehyde-modified bovine serum albumin (GA-BSA) decreased leptin expression at both the protein and mRNA levels in 3T3-L1 adipocytes and mouse epididymal adipocytes. The binding to and subsequent endocytic degradation of GA-BSA by 3T3-L1 adipocytes were effectively inhibited by a neutralizing anti-CD36 antibody. These results indicate that the ligand interaction of GA-BSA with CD36 leads to downregulation of leptin expression in 3T3-L1 adipocytes, suggesting that AGE-induced leptin downregulation is linked to reduction of the insulin sensitivity in metabolic syndrome.
Unno
Yuka
Y
Department of Medical Biochemistry, Kumamoto University Graduate School of Medical and Pharmaceutical sciences, Honjo 1-1-1, Kumamoto 860-8556, Japan. 027m5112@med.stud.kumamoto-u.ac.jp
Sakai
Masakazu
M
Sakamoto
Yu-Ichiro
Y
Kuniyasu
Akihiko
A
Nagai
Ryoji
R
Nakayama
Hitoshi
H
Horiuchi
Seikoh
S
D016475:3T3 Cells; D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000097:blood; D017667:Adipocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D000818:Animals; D018955:CD36 Antigens / Q000502:physiology*; D018929:Cell Culture Techniques; D005786:Gene Expression Regulation / Q000187:drug effects; D020738:Leptin / Q000235:genetics*; D024821:Metabolic Syndrome / Q000503:physiopathology; D051379:Mice; D047495:PPAR gamma / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D054411:Receptors, Leptin; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012710:Serum Albumin, Bovine / Q000494:pharmacology*
D018955:CD36 Antigens; D020738:Leptin; D047495:PPAR gamma; D012333:RNA, Messenger; D054411:Receptors, Leptin; C515447:leptin receptor, mouse; D012710:Serum Albumin, Bovine; D000079:Acetaldehyde; C010972:glycolaldehyde