FOXO1 suppresses PGC‐1β gene expression in skeletal muscles

Abstract

Peroxisome proliferator‐activated receptor‐gamma coactivator‐1β (PGC‐1β) is a transcriptional regulator whose increased expression activates energy expenditure‐related genes in skeletal muscles. However, how PGC‐1β is regulated remains largely unclear. Here, we show that PGC‐1β gene expression is negatively correlated with the expression of a transcription factor, forkhead box protein O1 (FOXO1), whose expression is increased during muscle atrophy. In the skeletal muscles of FOXO1‐overexpressing transgenic mice, PGC‐1β gene expression is decreased. Denervation or plaster cast‐based unloading, as well as fasting, increases endogenous FOXO1 expression in skeletal muscles, with decreased PGC‐1β expression. In the skeletal muscles of FOXO1‐knockout mice, the decrease in PGC‐1β expression caused by fasting was attenuated. Tamoxifen‐inducible FOXO1 activation in C2C12 myoblasts causes a marked decrease of PGC‐1β expression. These findings together reveal that FOXO1 activation suppresses PGC‐1β expression. During atrophy with FOXO1 activation, decreased PGC‐1β may decrease energy expenditure and avoid wasting energy.

Keywords

• atrophy
• FOXO1
• PGC‐1β
• skeletal muscle
• transcriptional factor