The Liver Clock Tunes Transcriptional Rhythms in Skeletal Muscle to Regulate Mitochondrial Function

Area of Science:

• Chronobiology
• Metabolic Physiology
• Endocrinology

Background:

• Circadian clocks regulate physiological processes for homeostasis.
• The skeletal muscle clock affects liver metabolism, but the liver clock's impact on muscle is unknown.

Purpose of the Study:

• To investigate the influence of the liver clock on skeletal muscle gene expression and metabolism.
• To uncover potential interorgan signaling axes in circadian regulation.

Main Methods:

• Utilized male hepatocyte-specific Bmal1 knockout (Bmal1^hep-/-) mice.
• Analyzed transcript oscillations in skeletal muscle.
• Treated myotubes with serum from knockout and wild-type mice.

Main Results:

• Approximately one-third of skeletal muscle transcript rhythms are influenced by the liver clock.
• Serum from Bmal1^hep-/- mice inhibited metabolic gene expression and lowered mitochondrial ATP production in myotubes.
• Liver clock-driven endocrine communication fine-tunes metabolic gene expression in muscle.

Conclusions:

• The liver clock communicates with skeletal muscle, establishing a bidirectional endocrine pathway.
• This liver-muscle clock communication pathway may contribute to metabolic disruptions observed in circadian rhythm disorders.