Serum amyloid A protein regulates the expression of genes related to lipid metabolism
Date Issued
2007
Date
2007
Author(s)
Chen, Chia-Hung
DOI
zh-TW
Abstract
Serum amyloid A protein (SAA) is an apolipoprotein, whose concentration increases during acute inflammation, and can replace apolipoprotein A1 (apoA1), the major apolipoprotein of HDL. Porcine SAA mRNA is increased by dietary docosahexaenoic acid (DHA) treatment. The purpose of this study was to investigate the role of SAA protein in regulating gene expression related to lipid metabolism in pigs. In the first experiment, human cell line, HepG2, was treated with 2 μM SAA for 3 days. Microarray technology was utilized to explore candidate genes regulated by the SAA treatment. The SAA down-regulated several genes involved in fatty acid metabolism, including transcription factors peroxisome proliferator-activated receptor α (PPARα, P<0.01) and hepatocyte nuclear factor 4α (HNF4α, P<0.01). Fatty acid synthase, acyl-CoA oxidase, and liver type fatty acid binding protein were also repressed by the SAA treatment, suggesting that SAA may exert its effects by suppressing the expression of PPARα to modify the expression of aforementioned genes. In order to further extend understandings about the role of SAA in pigs, porcine liver was first demonstrated abundant SAA gene expression. In the next study, porcine SAA gene was cloned from the liver showing that there is a signal peptide sequence, a strong evidence for porcine SAA as a secretory protein. Construction of the recombinant protein expression system in pQE-31 vector to express porcine SAA in E. coli. (M15 strain) was conducted. The addition of porcine SAA recombinant protein (pSAA) in porcine preadipocyte culture stimulated interleukin-6 (IL-6) mRNA expression (P<0.05), indicating a similar biological function of porcine SAA as compared with that in human. Peroxisome proliferator-activated receptor α (PPARα) and PPARγ mRNA was decreased by 40% and 60%, respectively, in differentiated adipocytes when treated with 2 μM pSAA. In addition, the SAA treatment caused a dramatic increase of inflammatory cytokine gene expressions (e.g., IL-6), and glycerol release, indicating an increase of lipolysis. Because the expression of perilipin, a lipid droplet-protective protein, was reduced by the SAA treatment, and the reduced perilipin would increase hormone sensitive lipase (HSL) activity, the increase of lipolysis by the SAA treatment may be mediated by decreasing perilipin.
In conclusion, the present study demonstrated that SAA can affect the expression of lipid metabolism related transcription factors in HepG2 cells. In pigs, the DHA-induced SAA gene expression decrease PPAR expression and therefore, down-regulates the target genes expression. Accordingly, SAA may play a critical role in mediating the function of dietary DHA on lipid metabolism.
Subjects
血清澱粉狀蛋白A
脂肪細胞
二十二碳六烯酸
serum amylois A
adipocyte
docosahexaenoic acid
Type
thesis
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