Estrogen-related receptor α modulates the expression of adipogenesis-related genes during adipocyte differentiation

Estrogen-related receptor α (ERRα) 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 ERRα in adipogenesis and white adipose tissue development has not been well studied. Here, we show that ERRα and ERRα-related transcriptional coactivators, peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α) and PGC-1β, 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 ERRα-specific siRNA results in mRNA down-regulation of fatty acid binding protein 4, PPARγ, and PGC-1α in 3T3-L1 cells in the adipogenesis medium. ERRα and PGC-1β 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 ERRα in 3T3-L1 cells up-regulates adipogenic marker genes and promotes triglyceride accumulation during 3T3-L1 differentiation. These results suggest that ERRα may play a critical role in adipocyte differentiation by modulating the expression of various adipogenesis-related genes.