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Serum Amyloid A Induces Lipolysis by Downregulating Perilipin Through ERK1/2 and PKA Signaling Pathways
Author(s) -
Liu Lih R.,
Lin Shau P.,
Chen Chih C.,
Chen Yu J.,
Tai Chen C.,
Chang Shih C.,
Juang Rong H.,
Tseng Yi W.,
Liu Bing H.,
Mersmann Harry J.,
Shen Tang L.,
Ding Shih T.
Publication year - 2011
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1038/oby.2011.176
Subject(s) - perilipin , lipolysis , hormone sensitive lipase , adipose triglyceride lipase , mapk/erk pathway , medicine , adipocyte , endocrinology , protein kinase a , chemistry , phosphorylation , kinase , protein kinase b , signal transduction , adipose tissue , biology , biochemistry
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.