Topical ER36009, a RARgamma-selective retinoid, decreases abdominal white adipose tissue and elicits changes in expression of genes related to adiposity and thermogenesis.
Chronic topical treatment of rats with a new RARgamma-selective retinoid, ER36009, resulted in a significant reduction of epididymal white adipose tissue and a significant increase of interscapular brown adipose tissue without affecting food intake. ER36009 markedly decreased PPARgamma, 11beta-HSD1, and Bcl-2 mRNA levels, and increased Bax mRNA in white adipose tissue, while it upregulated UCP1 and UCP3 mRNAs in brown adipose tissue and UCP3 mRNA in gastrocnemial muscle. These results suggest that ER36009 has multiple effects on adipose tissue biology and the energy balance. Topically applied ER36009 may have potential for the treatment of obesity.
Sakuta
Tomohiro
T
Shiseido Pharmaceutical Research Center, 2-12-1 Kanazawa-ku Fukuura, Yokohama, Japan 236-8643. tomohiro.sakuta@to.shiseido.co.jp
Uchiyama
Taro
T
Kanayama
Toshiji
T
D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000096:biosynthesis / Q000235:genetics; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism; D052436:Adipose Tissue, White / Q000187:drug effects* / Q000378:metabolism; D050154:Adiposity / Q000187:drug effects* / Q000235:genetics; D000818:Animals; D015152:Blotting, Northern; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D004435:Eating / Q000187:drug effects / Q000502:physiology; D007473:Ion Channels / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D024101:Mitochondrial Proteins / Q000096:biosynthesis / Q000235:genetics; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D011810:Quinoxalines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D022722:Thermogenesis / Q000187:drug effects / Q000235:genetics; D013844:Thiazoles / Q000494:pharmacology*; D000071256:Uncoupling Protein 1; D000071247:Uncoupling Protein 3; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000235:genetics
C516309:4-(4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-quinoxalinyl)-1,3-thiazol-2-yl)benzoic acid; C494828:Bax protein, rat; D007473:Ion Channels; D024101:Mitochondrial Proteins; D047495:PPAR gamma; D019253:Proto-Oncogene Proteins c-bcl-2; D011810:Quinoxalines; D012333:RNA, Messenger; D013844:Thiazoles; C000604373:Ucp1 protein, rat; C000604394:Ucp3 protein, rat; D000071256:Uncoupling Protein 1; D000071247:Uncoupling Protein 3; D051028:bcl-2-Associated X Protein; D042842:11-beta-Hydroxysteroid Dehydrogenases