Regulation of adipocyte differentiation by histone deacetylase inhibitors.
In this study, we investigated the effects of various histone deacetylase (HDAC) inhibitors on adipocyte differentiation. Treatment of 3T3-L1 cells with HDAC inhibitors such as apicidin, trichostatin A, or suberoylanilide hydroxamic acid, under conditions that normally promote differentiation led to a dramatic attenuation of adipocyte differentiation. In contrast, sodium butyrate (NaB) treatment increased adipocyte differentiation. Accordingly, the expression of adipogenic marker genes such as FAS, aP2, PPARgamma, resistin, C/EBPalpha, ADD1/SREBP1c, and adiponectin were inhibited by apicidin treatment but not NaB, indicating that the adipocyte differentiation process could be differentially regulated depending on the type of HDAC inhibitor utilized. In addition, this differential effect seemed not to be due to disruption of the insulin- signaling pathway. Interestingly, our data showed that apicidin treatment could induce dedifferentiation of fully differentiated adipocytes, as evident by the fact that apicidin treatment led to a decrease of Oil Red O-stained adipocytes with a concomitant reduction in the expression levels of adipogenic marker genes. Collectively, our results suggest that adipocyte differentiation and dedifferentiation may be regulated by HDAC inhibitors.
Kim
Su-Nam
SN
KIST Gangneung Institute, Gangneung, 210-340, Korea.
Choi
Hye-Young
HY
Kim
Yong Kee
YK
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000201:enzymology; D050156:Adipogenesis / Q000187:drug effects* / Q000235:genetics; D000818:Animals; D002087:Butyrates / Q000494:pharmacology; D054337:Cell Dedifferentiation / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D051379:Mice; D010456:Peptides, Cyclic / Q000494:pharmacology; D014280:Triglycerides / Q000378:metabolism; D000077337:Vorinostat
D002087:Butyrates; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007328:Insulin; D010456:Peptides, Cyclic; D014280:Triglycerides; C102351:apicidin; C012589:trichostatin A; D000077337:Vorinostat; D006655:Histone Deacetylases