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Biochemical, Molecular, and Genetic Mechanisms

Serum Amyloid A Protein Regulates the Expression of Porcine Genes Related to Lipid Metabolism^1–3,

Department of Animal Science and Technology, Institute of Biotechnology, National Taiwan University, Taipei 106, Taiwan

^* To whom correspondence should be addressed. E-mail: sding{at}ntu.edu.tw.

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-µmol/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 PPAR and PPAR mRNA were decreased (40 and 60%, respectively) in differentiated adipocytes after treatment with 2 µmol/L SAA. SAA treatment also increased inflammatory cytokine gene expression (IL-6 and tumor necrosis factor ) 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.