The prevention of adipose differentiation of 3T3-L1 cells caused by retinoic acid is elicited through retinoic acid receptor alpha.
Retinoids, especially all-trans retinoic acid (RA), have been shown to inhibit the differentiation of preadipose cells. It is important to human health, especially to obesity, that the regulatory system for the differentiation of adipocytes is well defined. Previously, we have shown that retinoic acid receptor (RAR) gamma 2 gene expression is up-regulated by RA in 3T3-L1 preadipose cells. In this study, the RAR system was dissected and the RA-regulated function in 3T3-L1 cells was assigned to one given receptor. We used three synthetic retinoids; (1) Ro 41-5253, a selective RAR alpha antagonist, (2) Ch 55, an RAR alpha, beta and gamma agonist, and (3) Am 80, an RAR alpha and beta agonist, which has less affinity to RAR gamma. Ro 41-5253 reverted RA-induced inhibition of the differentiation of 3T3-L1 cells. However, there was no significant reversion in RA-induced RAR gamma mRNA level by treatment with Ro 41-5253. In the case of RAR agonists, both Am 80 and Ch 55 strongly inhibited the differentiation of 3T3-L1 cells. However, Am 80 weakly increased RAR gamma mRNA content less than did Ch 55. These findings suggest, that RAR alpha is involved in the prevention of adipose differentiation by RA in 3T3-L1 cells. Moreover, there seems no causal relationship between the prevention of adipose differentiation by RA and the up-regulation of RAR gamma 2 gene expression by RA in 3T3-L1 cells. We have shown the functional heterogeneity of RA action through different RARs in 3T3-L1 cells.
Kamei
Y
Y
Department of Food Science and Technology, Faculty of Agriculture, Kyoto University, Japan.
Kawada
T
T
Mizukami
J
J
Sugimoto
E
E
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects*; D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002599:Chalcone / Q000031:analogs & derivatives / Q000494:pharmacology; D047188:Chalcones; D002839:Chromans / Q000494:pharmacology; D051379:Mice; D018168:Receptors, Retinoic Acid / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000072482:Retinoic Acid Receptor alpha; D012176:Retinoids / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology*
D001565:Benzoates; D047188:Chalcones; D002839:Chromans; C000607071:RARA protein, human; C000607072:Rara protein, mouse; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D012176:Retinoids; D013764:Tetrahydronaphthalenes; C061133:tamibarotene; C084904:Ro 41-5253; D014212:Tretinoin; D002599:Chalcone; C054189:3,5-di-tert-butylchalcone 4'-carboxylic acid