title: 15-Deoxy-delta(12,14) prostaglandin J2: a putative endogenous promoter of adipogenesis suppresses the ob gene.
abstract: Leptin is considered a key factor in the regulation of appetite and energy expenditure, but little is known about the control of its synthesis and release. Thiazolidinediones (TZDs) have recently been shown to downregulate leptin expression, and it has been speculated that downregulation of the ob gene occurs through activation of the transcription factor, peroxisome proliferator-activated receptor gamma (PPARgamma). However, there are no studies using an endogenous PPARgamma ligand. We examined the effect of 15-deoxy-delta(12,14) prostaglandin J2 (15d-PGJ2), a putative natural ligand of PPARgamma, on ob gene expression in fully differentiated 3T3-L1 adipocytes and compared its effect with that of two other PPARgamma activators, the TZD troglitazone (Trog) and indomethacin (Indo). 15d-PGJ2, Trog, and Indo all inhibited leptin expression at concentrations at which they activate PPARgamma. The inhibition of leptin expression of PPARgamma activators was surprising, since PPARgamma is known to induce adipogenesis during which the ob gene is expressed. To address the possibility that PPARgamma plays different roles before and after the induction of adipogenesis, we examined the effects of the three PPARgamma ligands on the expression of leptin and the glucose transporter protein GLUT4, both of which are expressed during differentiation of 3T3-L1 preadipocytes to adipocytes. In the absence of PPARgamma ligands, leptin and GLUT4 synthesis increased from day 3 to day 9 or 10 during differentiation. However, in the presence of any of the three PPARgamma ligands, GLUT4 expression was unaffected, while ob gene expression was inhibited. We hypothesize that PPARgamma may be essential for induction of adipocyte differentiation but then needs to be inactivated to allow expression of the ob gene.
authors.affiliation: Division of Endocrinology/Diabetes/Metabolism and the General Clinical Research Center, Temple University School of Medicine, Philadelphia, PA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Sinha
authors.forename: S
authors.initials: S
authors.lastname: Addya
authors.forename: E
authors.initials: E
authors.lastname: Murer
authors.forename: G
authors.initials: G
authors.lastname: Boden
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D051275:Glucose Transporter Type 4; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology*; D020738:Leptin; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins; D009687:Nuclear Proteins / Q000378:metabolism; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D011506:Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000378:metabolism*; D000077288:Troglitazone
chemical_list: C097240:15-deoxy-delta(12,14)-prostaglandin J2; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002839:Chromans; D004268:DNA-Binding Proteins; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D020738:Leptin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D009687:Nuclear Proteins; D011506:Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; C495692:SLC2A4 protein, human; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077288:Troglitazone; D015230:Prostaglandin D2; D007213:Indomethacin