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Glycolaldehyde‐Modified Bovine Serum Albumin Downregulates Leptin Expression in Mouse Adipocytes via a CD36‐Mediated Pathway
Author(s) -
UNNO YUKA,
SAKAI MASAKAZU,
SAKAMOTO YUICHIRO,
KUNIYASU AKIHIKO,
NAGAI RYOJI,
NAKAYAMA HITOSHI,
HORIUCHI SEIKOH
Publication year - 2005
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1333.080
Subject(s) - cd36 , scavenger receptor , leptin , chemistry , downregulation and upregulation , endocrinology , medicine , adipocyte , receptor , adiponectin , bovine serum albumin , troglitazone , leptin receptor , glycation , adipose tissue , peroxisome proliferator activated receptor , biology , insulin , biochemistry , lipoprotein , insulin resistance , cholesterol , gene , obesity
A bstract : 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 γ (PPAR‐γ) in macrophages, whereas PPAR‐γ 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.