15-Deoxy-delta 12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma.
Regulation of adipose cell mass is a critical homeostatic process in higher vertebrates. The conversion of fibroblasts into cells of the adipose lineage is induced by expression of the orphan nuclear receptor PPAR gamma. This suggests that an endogenous PPAR gamma ligand may be an important regulator of adipogenesis. By assaying arachidonate metabolites for their capacity to activate PPAR response elements, we have identified 15-deoxy-delta 12, 14-prostaglandin J2 as both a PPAR gamma ligand and an inducer of adipogenesis. Similarly, the thiazolidinedione class of antidiabetic drugs also bind to PPAR gamma and act as potent regulators of adipocyte development. Thus, adipogenic prostanoids and antidiabetic thiazolidinediones initiate key transcriptional events through a common nuclear receptor signaling pathway. These findings suggest a pivotal role for PPAR gamma and its endogenous ligand in adipocyte development and glucose homeostasis and as a target for intervention in metabolic disorders.
Salk Institute for Biological Studies, La Jolla, California 92037, USA.
B M
BM
Forman
P
P
Tontonoz
J
J
Chen
R P
RP
Brun
B M
BM
Spiegelman
R M
RM
Evans
D016475:3T3 Cells; D017667:Adipocytes / Q000737:chemistry / Q000166:cytology*; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D011416:Complement Factor D; D004268:DNA-Binding Proteins / Q000235:genetics; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005347:Fibroblasts / Q000166:cytology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D018996:Myelin P2 Protein / Q000235:genetics; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D000077205:Pioglitazone; D015230:Prostaglandin D2 / Q000819:agonists / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D047488:Retinoid X Receptors; D000077154:Rosiglitazone; D012697:Serine Endopeptidases / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology; D015533:Transcriptional Activation / Q000187:drug effects*
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C082667:Fabp5 protein, mouse; C086936:Fabp7 protein, mouse; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D007004:Hypoglycemic Agents; D008024:Ligands; D018996:Myelin P2 Protein; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D011453:Prostaglandins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D011993:Recombinant Fusion Proteins; D047488:Retinoid X Receptors; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077154:Rosiglitazone; D012697:Serine Endopeptidases; D011416:Complement Factor D; C493491:complement factor D, mouse; D015230:Prostaglandin D2; D000077205:Pioglitazone