The nuclear receptors Rev-erbα and Rev-erbβ are transcription factors that function both as a core repressive component of the cell-autonomous circadian clock machinery. We conditionally depleted Rev-erbα and Rev-erbβ in skeletal muscles in mice to explore their function into energy metabolism. The conditionally knockout (KO) mice displayed glucose intolerance and reduced grip strength. The KO mice also had lower oxygen consumption and impaired glucose uptake during exercise, without alteration in the muscle fiber type composition, mitochondrial protein content, or home-cage locomotor activity. Transcriptional analysis in muscle revealed that Rev-erbs regulate many genes involved in fatty acid oxidation, glucose transportation, tricarboxylic acid (TCA) cycle, and BCAAs catabolism. These results demonstrate that muscle clock plays an important role in regulating the energy homeostasis for in skeletal muscles.
J. Liu: None. Z. Sun: None.
National Institutes of Health
