C/EBPε participates in all-trans retinoic acid induction of PI3Kγ in U937 cells via an intronic matrix attachment region sequence

ATRA (all-trans retinoic acid) regulates gene expression by binding as a ligand to its specific receptors like C/EBPε which is directly induced. In the U937 cell line, PI3Kγ is selectively induced over other PI3Ks by ATRA, although the mechanism is still unclear. Here, we show that C/EBPε and PI3Kγ are induced in U937 cells by ATRA both in levels of mRNA and protein. Reporter gene assay revealed that C/EBPε is able to interact with a previously identified 2 kb MAR (matrix attachment region) sequence in the last intron of PI3Kγ gene, and increases its linked heterogenous reporter gene expression. ChIP assay showed that induction of endogenous PI3Kγ is at least partially caused by enhanced, direct C/EBPε binding to a 15 bp sequence at nucleotides 1428–1442 within this MAR sequence, and EMSA analysis confirmed this binding in vitro. The results above collectively show that C/EBPε participates in ATRA induction of PI3Kγ.     

Rehmannia inhibits adipocyte differentiation and adipogenesis

Rehmannia glutinosa, a Traditional Chinese Medicine (TCM), has been used to increase physical strength. Here, we report that Rehmannia glutinosa extract (RE) inhibits adipocyte differentiation and adipogenesis. RE impairs differentiation of 3T3-L1 preadipocytes in a dose-dependent manner. At the molecular level, treatment with RE inhibits expression of the key adipocyte differentiation regulator C/EBPβ, as well as C/EBPα and the terminal marker protein 422/aP2, during differentiation of preadipocytes into adipocytes. Additionally, RE inhibits the mitotic clonal expansion (MCE) process of adipocyte differentiation, and RE prevents localization of C/EBPβ to the centromeres. RE also prevents high fat diet (HFD) induced weight gain and adiposity in rats. Taken together, our results indicate that Rehmannia glutinosa extract inhibits preadipocyte differentiation and adipogenesis in cultured cells and in rodent models of obesity.