High Mobility Group Box 1 Negatively Regulates Lipolysis in Adipocytes : Role of Caveolin-1

• Main Authors: Kuan-Ting Chiu, 邱冠霆
• Other Authors: Tzong-Shyuan Lee
• Format: Others
• Language: en_US
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/w72cax

碩士 === 國立陽明大學 === 生理學研究所 === 97 === Obesity　is　characterized　by　excess　fat　accumulation　in　white　adipose　tissue,　which　increases　the　risk　of　various　diseases.　Adipocytes　release　various　adipokines　such　as　adiponectin　to　regulate　lipid　homeostasis.　High　mobility　group　box　1　(HMGB1)　is　not　only　a　key　protein　for　stabilization　of　chromosome　and　regulation　of　transcription　in　nucleus,　but　also　released　into　the　extracellular　space　via　exocytosis　to　modulate　inflammatory　response.　However,　the　exact　role　and　underlying　mechanisms　of　HMGB1　in　adipogenesis　are　largely　unknown.　Caveolin-1　(Cav-1)　is　major　structure　protein　of　caveolae,　which　plays　a　crucial　role　in　lipid　metabolism　and　mediates　secretion,　internalization　and　vesicle　trafficking　of　proteins　by　interacting　with　intracellular　proteins.　In　the　present　study,　we　performed　in　vitro　and　in　vivo　experiments　to　explore　whether　Cav-1　interacts　with　HMGB1　to　regulate　adipogenesis.　Western　blotting　showed　that　the　levels　of　HMGB1,　Cav-1　and　phosphorylated　Cav-1　were　significantly　increased　during　differentiation　of　3T3-L1　adipocytes　in　a　time-dependent　manner.　HMGB1　treatment　did　not　affect　preadipocyte　proliferation　and　differentiation.　By　contrast,　starvation-　or　刍3-adrenoreceptor　agonist CL-induced　lipolysis　and　phosphorylation　of　hormone　sensitive　lipase　were　significantly　attenuated　upon　HMGB1　treatment　via　inhibition　on　activation　of　protein　kinase　A　and　extracellular　signal-regulated kinase　phosphorylation　in　3T3-L1　adipocytes.　We　also found　that　the　increases　in　release　of　HMGB1,　Cav-1 phosphorylation　and　interaction　between　HMGB1　and　Cav-1　were　Src　kinase-dependent,　as　revealed　by　its　abolition　after　inhibition　using　pharmacologic　inhibitors.　After　starvation　or　fasting,　secretion　of　HMGB1　was　increased　in　Cav-1　deficient　mouse　embryonic　fibroblast　and　mice　compared　to　wildtypes.　Collectively,　the　findings　suggest　that　HMGB1　plays　a　critical　role　in　adipocyte　lipolysis　via　interaction　with　Cav-1.