Docosahexaenoic acid enhances hepatic serum amyloid A expression via protein kinase A-dependent mechanism
Date Issued
2009
Date
2009
Author(s)
Tai, Chen-Chen
Abstract
Serum amyloid A (SAA) reduces fat deposition in adipocytes and hepatocytes. Human SAA1 mRNA is increased by docosahexaenoic acid (DHA) treatment in human cells. These studies asked whether DHA decreases fat deposition through SAA1 and explored the corresponding mechanisms. We demonstrated that DHA increased human SAA1 and C/EBPβ mRNA expression in human hepatoma cells, SK-HEP-1. Utilizing promoter deletion assay, we found that a C/EBPβ binding site in the SAA1 promoter region between -242 and -102 bp is critical for DHA-mediated SAA1 expression. When we mutated the putative C/EBPβ binding site, the DHA-induced SAA1 promoter activity was suppressed, suggesting that this binding sequence was very important for the DHA regulated transcription activation. The addition of the protein kinase A inhibitor, H89, negated the DHA-induced increase in C/EBPβ protein expression. The up-regulation of SAA1 mRNA and protein by DHA was inhibited by H89 treatment, as well. We further demonstrated that DHA increased protein kinase A (PKA) activities. These data suggest that C/EBPβ is involved in the DHA-regulated increase in SAA1 expression via PKA-dependent mechanisms. Furthermore, the suppressive effect of DHA on triacylglycerol accumulation was abolished by H89 treatment in hepatocytes and adipocytes indicating that DHA reduces lipid accumulation via PKA as well. The phenomena of increased SAA1 expression coupled with reduced fat accumulation mediated by DHA via PKA suggest that SAA1 is involved in DHA-induced triacylglycerol breakdown. These findings provide new insights into the complicated regulatory network in DHA-mediated lipid metabolism and may be useful in developing new therapeutic approaches to reduce body fat deposition and fatty liver.
Subjects
DHA
fatty liver
SAA
Type
thesis
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