Estrogen-related receptor alpha modulates the expression of adipogenesis-related genes during adipocyte differentiation.
Estrogen-related receptor alpha (ERRalpha) is an orphan nuclear receptor that regulates cellular energy metabolism by modulating gene expression involved in fatty acid oxidation and mitochondrial biogenesis in brown adipose tissue. However, the physiological role of ERRalpha in adipogenesis and white adipose tissue development has not been well studied. Here, we show that ERRalpha and ERRalpha-related transcriptional coactivators, peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator-1alpha (PGC-1alpha) and PGC-1beta, can be up-regulated in 3T3-L1 preadipocytes at mRNA levels under the adipogenic differentiation condition including the inducer of cAMP, glucocorticoid, and insulin. Gene knockdown by ERRalpha-specific siRNA results in mRNA down-regulation of fatty acid binding protein 4, PPARgamma, and PGC-1alpha in 3T3-L1 cells in the adipogenesis medium. ERRalpha and PGC-1beta mRNA expression can be also up-regulated in another preadipocyte lineage DFAT-D1 cells and a pluripotent mesenchymal cell line C3H10T1/2 under the differentiation condition. Furthermore, stable expression of ERRalpha in 3T3-L1 cells up-regulates adipogenic marker genes and promotes triglyceride accumulation during 3T3-L1 differentiation. These results suggest that ERRalpha may play a critical role in adipocyte differentiation by modulating the expression of various adipogenesis-related genes.
Ijichi
Nobuhiro
N
Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan.
Ikeda
Kazuhiro
K
Horie-Inoue
Kuniko
K
Yagi
Ken
K
Okazaki
Yasushi
Y
Inoue
Satoshi
S
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005786:Gene Expression Regulation; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D008809:Mice, Inbred C3H; D034741:RNA, Small Interfering / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D000097983:ERRalpha Estrogen-Related Receptor
D047628:Estrogen Receptor alpha; D034741:RNA, Small Interfering; D011960:Receptors, Estrogen; D000097983:ERRalpha Estrogen-Related Receptor