Artemisinic Acid is a Regulator of Adipocyte Differentiation and C/EBP δ Expression

Adipocyte dysfunction is associated with the development of obesity. In this study, artemisinic acid, which was isolated from Artemisia annua L, inhibited adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells (hAMSCs) and its mechanism of action was determined. The mRNA levels of peroxidase proliferation-activated receptor (PPAR) gamma and CCAAT/enhancer binding protein (C/EBP) alpha, late adipogenic factors, were reduced by artemisinic acid. Moreover, the mRNA levels of the PPAR gamma target genes lipoprotein lipase, CD36, adipocyte protein, and liver X receptor were down-regulated by artemisinic acid. Artemisinic acid reduced expression of the C/EBP delta gene without impacting C/EBP beta. In addition, attempts to elucidate a possible mechanism underlying the artemisinic acid-mediated effects revealed that reduced expression of the C/EBP delta gene was mediated by inhibiting Jun N-terminal kinase (JNK). Additionally, artemisinic acid also reduced the expression of the adipogenesis-associated genes glucose transporter-4 and vascular endothelial growth factor. In addition to the interference of artemisinic acid with adipogenesis, artemisinic acid significantly attenuated tumor necrosis factor-alpha-induced secretion of interleukin-6 by undifferentiated hAMSCs, thus influencing insulin resistance and the inflammatory state characterizing obesity. Taken together, these findings indicate that inhibiting adipogenic differentiation of hAMSCs by artemisinic acid occurs primarily through reduced expression of C/EBP delta, which is mediated by the inhibition of JNK and suggest that aremisinic acid maybe used as a complementary treatment option for obesity associated with metabolic syndrome. J. Cell. Biochem. 113: 2488-2499,2012. (C) 2012 Wiley Periodicals, Inc.