Identification of a Novel Function of Resveratrol and Genistein as a Regulator of β 2 -Adrenergic Receptor Expression in Skeletal Muscle Cells and Characterization of Promoter Elements Required for Promoter Activation

Modulating β -adrenergic receptor (β -AR) expression and activation is important for maintaining skeletal muscle function. In this study, two food factors, resveratrol (RSV) and genistein (GEN), that are able to regulate β -AR promoter activity and may improve skeletal muscle function are identified. Using luciferase reporter assay, 357 functional food factors as candidates for β -AR promoter activity have been screened and subsequently RSV and GEN increase β -AR promoter activity and β -AR mRNA expression. Using promoter sequence analysis, it is shown that the CCAAT box and the GC box on the β -AR promoter are required for the regulation of β -AR expression by RSV or GEN. It is also ascertained that transcription factor NF-YA binds to the CCAAT box on the β -AR promoter and that the amount of NF-YA bound to the CCAAT box is unchanged by RSV or GEN treatment. Finally, it is confirmed that a GEN-containing diet increases β -AR expression in mouse skeletal muscle and increased skeletal muscle mass. The findings show that food-derived molecules have the potential to influence skeletal muscle mass and function by regulating G protein-coupled receptor expression.