ABSTRACT
Docosahexaenoic acid (DHA) increases lipolysis and decreases lipogenesis through several pathways. DHA also enhances the expression of serum amyloid A protein (SAA), a possible lipid metabolism related gene. The question of whether DHA regulates the expression of SAA to affect lipid metabolism and increase lipolysis needs to be demonstrated in human adipocytes. We designed experiments to determine the role of SAA in regulating lipid metabolism in HepG2 cells using microarray technology. In human hepatocytes, recombinant human SAA1 (hSAA1) inhibited the expression of genes related to lipogenesis and promoted the expression of those involved in lipolysis. When human breast adipocytes were treated with hSAA1 or DHA in vitro, the expression of peroxisome proliferator-activated receptor gamma and other lipogenic genes was decreased, whereas the expression of several lipolytic genes was increased. Glycerol release was increased by both SAA and DHA treatments, suggesting that they increased lipolytic activity in human adipocytes. The expression of perilipin, a lipid droplet-protective protein, was decreased, and hormone-sensitive lipase was increased by both of hSAA1 and DHA treatment. We speculate that the mechanism of lipolysis by DHA or SAA is at least partially the result of increased expression of hormone-sensitive lipase and decreased expression of perilipin. Whereas DHA treatment increased expression of hSAA1 in human adipocytes, the DHA-mediated reduction in expression of lipogenesis genes and enhancement of lipolysis may be through the activity of hSAA1. These results may be useful in developing new approaches to reduce body fat deposition.
Subject(s)
Docosahexaenoic Acids/administration & dosage , Lipolysis , Phosphoproteins/metabolism , Serum Amyloid A Protein/physiology , Adipocytes, White/enzymology , Adipocytes, White/metabolism , Adipogenesis , Adipose Tissue, White/cytology , Adipose Tissue, White/enzymology , Adipose Tissue, White/metabolism , Carrier Proteins , Cells, Cultured , Down-Regulation , Female , Gene Expression Profiling , Gene Expression Regulation , Hep G2 Cells , Humans , Interleukin-6/genetics , Interleukin-6/metabolism , Lipogenesis , Oligonucleotide Array Sequence Analysis , Perilipin-1 , Phosphoproteins/genetics , Recombinant Proteins , Serum Amyloid A Protein/genetics , Sterol Esterase/genetics , Sterol Esterase/metabolism , Stromal Cells/metabolismABSTRACT
Serum amyloid A protein (SAA) is an apolipoprotein that can replace apolipoprotein A1 (apoA1) as the major apolipoprotein of HDL. Porcine hepatic 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. First, we demonstrated that the 100-micromol/L DHA treatment increased SAA and apoA1 mRNA expression in porcine hepatic cell cultures (P < 0.05). Secondly, we produced porcine SAA recombinant protein and found that the addition of SAA to porcine preadipocytes in culture stimulated interleukin-6 (IL-6) mRNA expression (P < 0.05), indicating a similar biological function of porcine SAA and human SAA. We also found PPARalpha and PPARgamma mRNA were decreased (40 and 60%, respectively) in differentiated adipocytes after treatment with 2 mumol/L SAA. SAA treatment also increased inflammatory cytokine gene expression (IL-6 and tumor necrosis factor alpha) and glycerol release (P < 0.05), indicating increased lipolysis. Because the expression of perilipin, a lipid droplet-protective protein, was reduced by the SAA treatment, we hypothesized that SAA increased lipolysis by decreasing the expression of perilipin, which would then allow an increase in hormone sensitive lipase activity. In conclusion, we demonstrated that the DHA-induced SAA gene expression decreased PPAR expression and consequently downregulated the expression of several genes involved in lipid metabolism. Accordingly, SAA may play a critical role in mediating the function of dietary DHA on lipid metabolism and could be a factor in regulating obesity.
