Serum amyloid A induced lipolysis signal transduction pathway
Date Issued
2009
Date
2009
Author(s)
Liu, Li-Ru
Abstract
Serum amyloid A protein (SAA) is not only an apolipoprotein, but also a member of adipokines with potentials to enhance lipolysis in human and porcine adipocytes. The purpose of this study was to explore how SAA facilitates lipolysis in porcine adipocytes. Several predict signal transducer inhibitors and porcine SAA recombinant protein were used to treat porcine adipocytes in primary cell culture. We found SAA decreased the expression of perilipin, hormone sensitive lipase (HSL), and adipose triacylglycerol lipase (ATGL) mRNA and such effect could be recovered by extracellular signal-regulated kinase (ERK) and/or protein kinase A (PKA) inhibitors. The SAA also activates ERK and PKA via phosphorylating these kinases in porcine adipocytes. Moreover, SAA increased porcine adipocyte glycerol release, which was abrogated by ERK (PD98059) and PKA (H89) inhibitor, suggesting that ERK and PKA involve in mediating the SAA enhanced lipolysis. On the other hand, SAA down-regulated the expression of peroxisome proliferator-activated receptors gamma (PPARγ) mRNA which was recovered by ERK inhibitor. To understand whether PPARγ participates in SAA promoted lipolysis via ERK, we performed the porcine perilipin promoter assay with luciferase as promoter in differentiated 3T3L1 adipocytes. We found that SAA reduced porcine perilipin promoter specifically through the function of its PPARγ response element (PPRE), and this effect was recovered by ERK inhibitor. However, PKA did not have a role in the SAA regulated PPRE activity. These findings demonstrate that SAA induced lipolysis is a result of down-regulation of perilipin via ERK/PPARγ and PKA signaling pathways which are novel pathways by which SAA directly stimulates lipolysis to liberate glycerol efflux from adipocytes.
Subjects
lipolysis
Type
thesis
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