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.
journal_name
FEBS Open Biojournal_title
FEBS open bioauthors
Nakai S,Oyabu M,Hatazawa Y,Akashi S,Kitamura T,Miura S,Kamei Ydoi
10.1002/2211-5463.12898subject
Has Abstractpub_date
2020-07-01 00:00:00pages
1373-1388issue
7issn
2211-5463journal_volume
10pub_type
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