Synergistic potentiation of thiazolidinedione-induced ST 13 preadipocyte differentiation by RAR synergists.
Peroxisome proliferator-activated receptor gamma (PPAR gamma) belongs to a nuclear receptor super family that functions as a master regulator of adipocyte differentiation. PPAR gamma binds its DNA response element together with a partner, retinoid X receptor (RXR), in fat cells. Five RXR ligands (HX600, HX630, DA022, DA124, LGD1069, referred to as retinoid synergists) by themselves exhibit weak transactivation activity on the PPAR gamma response element. However, addition of PPAR gamma-specific ligand in this assay gave rise to a 5- to 13-fold increase, indicating a strong synergy between these ligands. LGD1069 was the most effective activator of the RXR/PPAR gamma heterodimer on the transactivation of the reporter gene. But, in contrast to the other four RXR ligands, LGD1069 did not show synergistic induction of ST 13 preadipocytes to adipocytes. This apparent contradiction may result from the ligand-binding property of LGD1069. In this article we discuss the fact that retinoid synergists also act as PPAR gamma synergists.
Sato
M
M
Pharmaceutical Research and Development Center, Tokyo Metropolitan Institute for Medical Science, 18-22, Honkomagome 3-chome, Bunkyo-ku, Tokyo 113-8613, Japan.
Yajima
Y
Y
Kawashima
S
S
Tanaka
K
K
Kagechika
H
H
D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D062365:Aminobenzoates / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology; D001565:Benzoates / Q000008:administration & dosage / Q000494:pharmacology; D000077610:Bexarotene; D002454:Cell Differentiation; D002460:Cell Line; D003984:Dibenzazepines / Q000008:administration & dosage / Q000494:pharmacology; D008024:Ligands; D051379:Mice; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D047488:Retinoid X Receptors; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000494:pharmacology; D013844:Thiazoles / Q000008:administration & dosage / Q000494:pharmacology*; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D062365:Aminobenzoates; D001552:Benzazepines; D001565:Benzoates; C422176:DA 022; C422177:DA 124; D003984:Dibenzazepines; C422175:HX 630; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D013764:Tetrahydronaphthalenes; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; C104181:HX 600; D000077610:Bexarotene; C039671:ciglitazone