Inhibition of adipose differentiation by 9 alpha, 11 beta-prostaglandin F2 alpha.
Prostaglandin F2 alpha (PGF2 alpha) is a potent adipose differentiation inhibitor for the adipogenic cell line 1246 and for adipocyte precursors in primary culture with an ED50 of 3 x 10(-8) M. In this paper, we examined the effect of several prostaglandins which have structural similarities with PGF2 alpha on the differentiation of 1246 cells and of adipocyte precursors in primary culture. The results show that only 9 alpha,11 beta-PGF2 alpha is as potent as PGF2 alpha to inhibit differentiation of adipocyte precursors in primary culture and of the adipogenic cell line 1246. In the presence of 9 alpha,11 beta-PGF2 alpha, the cells remained fibroblast-like, typical of undifferentiated adipocyte precursors. Triglyceride accumulation and increase of specific activity for glycerol-3-phosphate dehydrogenase were inhibited. In addition, mRNA expression of early markers of differentiation such as lipoprotein lipase (LPL) and fatty acid binding protein (FAB) was decreased. The isomer 9 beta,11 alpha-PGF2 alpha and other PGF2 alpha derivatives were inactive. These results provide new information on the biological activity of 9 alpha,11 beta-PGF2 alpha as an inhibitor of adipose differentiation and about the structural characteristics of prostaglandins required for maintenance of a high adipose differentiation inhibitory effect.
Lepak
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W. Alton Jones Cell Science Center, Inc., Lake Placid, NY 12946.
Serrero
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D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D008049:Lipase / Q000235:genetics; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013329:Structure-Activity Relationship; D014280:Triglycerides / Q000378:metabolism
D002352:Carrier Proteins; C490174:Fabp7 protein, rat; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D014280:Triglycerides; D015237:Dinoprost; D005954:Glucosephosphate Dehydrogenase; D008049:Lipase