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.

中文翻译：

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FOXO1 抑制骨骼肌中 PGC-1β 基因的表达。

过氧化物酶体增殖物激活受体-γ共激活因子-1β（PGC-1β）是一种转录调节因子，其表达增加激活骨骼肌中与能量消耗相关的基因。然而，PGC-1β 的调控方式在很大程度上仍不清楚。在这里，我们表明 PGC-1β 基因表达与转录因子叉头盒蛋白 O1 (FOXO1) 的表达呈负相关，其表达在肌肉萎缩期间增加。在 FOXO1 过表达转基因小鼠的骨骼肌中，PGC-1β 基因表达降低。去神经支配或基于石膏模型的卸载以及禁食会增加骨骼肌中内源性 FOXO1 的表达，同时降低 PGC-1β 的表达。在 FOXO1 基因敲除小鼠的骨骼肌中，禁食引起的 PGC-1β 表达降低减弱。C2C12 成肌细胞中他莫昔芬诱导的 FOXO1 激活导致 PGC-1β 表达显着降低。这些发现共同表明 FOXO1 激活抑制 PGC-1β 表达。在 FOXO1 激活的萎缩过程中，降低的 PGC-1β 可能会减少能量消耗并避免浪费能量。