Modulation of adipogenesis-related gene expression by estrogen-related receptor γ during adipocytic differentiation

Estrogen-related receptor γ (ERRγ) is an orphan nuclear receptor that regulates cellular energy metabolism by modulating gene expression involved in oxidative metabolism and mitochondrial biogenesis in brown adipose tissue and heart. However, the physiological role of ERRγ in adipogenesis and the development of white adipose tissue has not been well studied. Here we show that ERRγ was up-regulated in murine mesenchyme-derived cells, especially in ST2 and C3H10T1/2 cells, at mRNA levels under the adipogenic differentiation condition including the inducer of cAMP, glucocorticoid, and insulin. The up-regulation of ERRγ mRNA was also observed in inguinal white adipose and brown adipose tissues of mice fed a high-fat diet. Gene knockdown by ERRγ-specific siRNA results in mRNA down-regulation of adipogenic marker genes including fatty acid binding protein 4, PPARγ, and PGC-1β in a preadipocyte cell line 3T3-L1 preadipocytes and mesenchymal ST2 and C3H10T1/2 cells in the adipogenesis medium. In contrast, stable expression of ERRγ in 3T3-L1 cells resulted in up-regulation of these adipogenic marker genes under the adipogenic condition. These results suggest that ERRγ positively regulate the adipocyte differentiation with modulating the expression of various adipogenesis-related genes.