Serum amyloid A (SAA) is not only an apolipoprotein, but also a member of the adipokine family with potential to enhance lipolysis. The purpose of this study was to explore how SAA facilitates lipolysis in porcine adipocytes. We found that SAA increased the phosphorylation of perilipin and hormone‐sensitive lipase (HSL) after 12‐h treatment and decreased perilipin expression after 24‐h treatment, and these effects were prevented by extracellular signal‐regulated kinase (ERK) or protein kinase A (PKA) inhibitors in primary adipocyte cell culture. SAA treatment decreased HSL and adipose triglyceride lipase (ATGL) expression. SAA treatment also activated ERK and PKA by increasing the phosphorylation of these kinases. Moreover, SAA significantly increased porcine adipocyte glycerol release and lipase activity, which was inhibited by either ERK (PD98059) or PKA (H89) inhibitors, suggesting that ERK and PKA were involved in mediating SAA enhanced lipolysis. SAA downregulated the expression of peroxisome proliferator‐activated receptor γ (PPARγ) mRNA, which was reversed by the ERK inhibitor. We performed a porcine perilipin promoter assay in differentiated 3T3–L1 adipocytes and found that SAA reduced the porcine perilipin promoter specifically through the function of its PPAR response element (PPRE), and this effect was reversed by the ERK inhibitor. These findings demonstrate that SAA‐induced lipolysis is a result of downregulation of perilipin and activation of HSL via ERK/PPARγ and PKA signaling pathways. The finding could lead to developing new strategies for reducing human obesity.
Using suppression subtractive hybridization technique, we found that 2 novel genes (AEUG1 and AEUG3) were highly expressed in the adipocytes compared with preadipocytes. We then identified that these 2 genes were both angiotensin-converting enzyme 2 (ACE2). We applied 3'RACE (rapid amplification of cDNA end), 5'RACE, and PCR to obtain the full-length porcine ACE2 cDNA sequence. Because eicosanoids derived from PUFA are involved in regulating blood pressure, we hypothesized that PUFA can regulate the expression of the vasodilator ACE2. Preadipocytes from Landrace pigs were induced to differentiate for 4 d, then treated with 50 μM of different PUFA, CLA, arachidonic acid, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or stearic acid (18:0). Addition of EPA or 18:0 for 48 h did not change the ACE2 mRNA abundance, whereas the treatments of arachidonic acid, CLA, and DHA significantly decreased ACE2 mRNA abundance after 48 h (P ≤ 0.05). Treatment with PUFA did not change (P > 0.05) type I and type II angiotensin receptor mRNA abundance. To further understand how PUFA metabolites affect ACE2 mRNA expression, we inhibited individual enzymes that are involved in eicosanoid production. We found that 3 individual eicosanoid pathway enzyme inhibitors recovered the PUFA effect on the expression of ACE2, indicating these pathways are involved in mediating the PUFA function. In conclusion, we obtained the full-length porcine ACE2 cDNA sequence and found PUFA could downregulate the expression of ACE2 through its metabolites without changing the expression of their receptor in porcine adipocytes.
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