title: Artemisinic acid is a regulator of adipocyte differentiation and C/EBP δ expression.
abstract: 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) γ and CCAAT/enhancer binding protein (C/EBP) α, late adipogenic factors, were reduced by artemisinic acid. Moreover, the mRNA levels of the PPAR γ 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 δ gene without impacting C/EBP β. In addition, attempts to elucidate a possible mechanism underlying the artemisinic acid-mediated effects revealed that reduced expression of the C/EBP δ 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-α-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 δ, which is mediated by the inhibition of JNK and suggest that aremisinic acid may be used as a complementary treatment option for obesity associated with metabolic syndrome.
authors.affiliation: Department of Dermatological Health Management, Eul-Ji University, Seongnam City, Gyunggi Do, Republic of Korea.
authors.forename: Jongsung
authors.initials: J
authors.lastname: Lee
authors.forename: Moo-Han
authors.initials: MH
authors.lastname: Kim
authors.forename: Jin-Hyuck
authors.initials: JH
authors.lastname: Lee
authors.forename: Eunsun
authors.initials: E
authors.lastname: Jung
authors.forename: Eun-Sook
authors.initials: ES
authors.lastname: Yoo
authors.forename: Deokhoon
authors.initials: D
authors.lastname: Park
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D050156:Adipogenesis / Q000187:drug effects*; D037621:Artemisinins / Q000494:pharmacology*; D051743:CCAAT-Enhancer-Binding Protein-delta / Q000096:biosynthesis*; D018955:CD36 Antigens / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation; D002460:Cell Line; D015536:Down-Regulation; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D050556:Fatty Acid-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D051275:Glucose Transporter Type 4 / Q000096:biosynthesis; D006801:Humans; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D008071:Lipoprotein Lipase / Q000096:biosynthesis / Q000235:genetics; D000071518:Liver X Receptors; D059630:Mesenchymal Stem Cells / Q000502:physiology; D009765:Obesity / Q000188:drug therapy*; D057093:Orphan Nuclear Receptors / Q000096:biosynthesis / Q000235:genetics; D047495:PPAR gamma / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D037621:Artemisinins; D018955:CD36 Antigens; D004365:Drugs, Chinese Herbal; D050556:Fatty Acid-Binding Proteins; D051275:Glucose Transporter Type 4; D015850:Interleukin-6; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D047495:PPAR gamma; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D051743:CCAAT-Enhancer-Binding Protein-delta; C047721:artemisic acid; D048031:JNK Mitogen-Activated Protein Kinases; D008071:Lipoprotein Lipase