title: D-dopachrome tautomerase promotes IL-6 expression and inhibits adipogenesis in preadipocytes.
abstract: We previously identified D-dopachrome tautomerase (DDT) as a novel adipokine whose mRNA levels in adipocytes are negatively correlated with obesity-related clinical parameters, and which acts on adipocytes to regulate lipid metabolism. Here we investigated functions of DDT on preadipocytes. Recombinant DDT (rDDT) enhanced both the expression and secretion of interleukin-6 (IL-6) in SGBS cells, a human preadipocyte cell line. Treatment with rDDT increased levels of phosphorylated ERK1/2, but not p38, in SGBS cells, and rDDT-induced IL-6 mRNA expression was attenuated by pretreatment with an ERK inhibitor, U0126. Knockdown of CD74, but not CD44, inhibited rDDT-induced IL-6 mRNA expression in SGBS cells. These results suggested that the rDDT-induced IL-6 expression in preadipocytes occurred through the CD74-ERK pathway. Furthermore, in SGBS cells subjected to adipogenic induction, rDDT decreased the amount of triacylglycerol, number of cells with oil droplets, and levels of mRNA encoding adipocyte marker proteins. Increased expression of CCAAT/enhancer binding protein families and peroxisome proliferator-activated receptor γ2 during adipogenesis was inhibited in the cells treated with rDDT. These results suggested DDT to inhibit adipogenesis by suppressing the expression of genes encoding adipogenic regulators in preadipocytes.
authors.affiliation: Department of Orthodontics and Dentofacial Orthopedics, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8504, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Ishimoto
authors.forename: Takeo
authors.initials: T
authors.lastname: Iwata
authors.forename: Hisaaki
authors.initials: H
authors.lastname: Taniguchi
authors.forename: Noriko
authors.initials: N
authors.lastname: Mizusawa
authors.forename: Eiji
authors.initials: E
authors.lastname: Tanaka
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Yoshimoto
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D050156:Adipogenesis / Q000502:physiology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000378:metabolism; D002070:Butadienes / Q000494:pharmacology; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D019746:Intramolecular Oxidoreductases / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D047495:PPAR gamma / Q000096:biosynthesis; D010766:Phosphorylation; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering; D011994:Recombinant Proteins / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D002070:Butadienes; D022762:CCAAT-Enhancer-Binding Proteins; D000949:Histocompatibility Antigens Class II; D018960:Hyaluronan Receptors; D015850:Interleukin-6; D009570:Nitriles; D047495:PPAR gamma; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D014280:Triglycerides; C113580:U 0126; C045084:invariant chain; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase