Serum amyloid A induces lipolysis by downregulating perilipin through ERK1/2 and PKA signaling pathways.
Resource
Obesity (Silver Spring),19(12),2301-2309.
OBESITY, 19(12), 2301-2309
Date Issued
2011-12
Author(s)
Liu, LR
Lin S.P.
Chen C.C.
Chen Y.J.
Tai C.C.
Chang S.C.
Juang R.H.
Tseng Y.W.
Liu B.H.
Mersmann H.J.
Shen T.L.
Abstract
Serum amyloid A (SAA) is not only an apolipoprotein, but also a member of the adipokine family with potential to enhance lipolysis. The purpose of this study was to explore how SAA facilitates lipolysis in porcine adipocytes. We found that SAA increased the phosphorylation of perilipin and hormone-sensitive lipase (HSL) after 12-h treatment and decreased perilipin expression after 24-h treatment, and these effects were prevented by extracellular signal-regulated kinase (ERK) or protein kinase A (PKA) inhibitors in primary adipocyte cell culture. SAA treatment decreased HSL and adipose triglyceride lipase (ATGL) expression. SAA treatment also activated ERK and PKA by increasing the phosphorylation of these kinases. Moreover, SAA significantly increased porcine adipocyte glycerol release and lipase activity, which was inhibited by either ERK (PD98059) or PKA (H89) inhibitors, suggesting that ERK and PKA were involved in mediating SAA enhanced lipolysis. SAA downregulated the expression of peroxisome proliferator-activated receptor γ (PPARγ) mRNA, which was reversed by the ERK inhibitor. We performed a porcine perilipin promoter assay in differentiated 3T3-L1 adipocytes and found that SAA reduced the porcine perilipin promoter specifically through the function of its PPAR response element (PPRE), and this effect was reversed by the ERK inhibitor. These findings demonstrate that SAA-induced lipolysis is a result of downregulation of perilipin and activation of HSL via ERK/PPARγ and PKA signaling pathways. The finding could lead to developing new strategies for reducing human obesity. ? 2011 The Obesity Society.
SDGs
Other Subjects
2 (2 amino 3 methoxyphenyl)chromone; cyclic AMP dependent protein kinase; glycerol; hormone sensitive lipase; messenger RNA; mitogen activated protein kinase 1; n [2 (4 bromocinnamylamino)ethyl] 5 isoquinolinesulfonamide; perilipin; peroxisome proliferator activated receptor gamma; serum amyloid A; triacylglycerol lipase; adipocyte; animal cell; article; cell differentiation; cell strain 3T3; controlled study; down regulation; enzyme activity; enzyme release; lipolysis; nonhuman; protein expression; protein function; protein phosphorylation; signal transduction; swine; 3T3-L1 Cells; Adipocytes; Animals; Carrier Proteins; Cyclic AMP-Dependent Protein Kinases; Down-Regulation; Extracellular Signal-Regulated MAP Kinases; Glycerol; Lipase; Lipolysis; Mice; Phosphoproteins; Phosphorylation; PPAR gamma; Response Elements; RNA, Messenger; Serum Amyloid A Protein; Signal Transduction; Sterol Esterase; Swine; Sus
Type
journal article