Control of circadian muscle glucose metabolism through the BMAL1-HIF axis in obesity.
Summary
Muscle-specific BMAL1 loss worsened glucose tolerance under high-fat diet without increased weight gain, implicating circadian control of skeletal muscle glucose metabolism in diet-induced obesity. The study identifies a BMAL1–HIF axis as a regulatory node linking clock function to metabolic reprogramming.
Key Findings
- Muscle-specific BMAL1 knockout mice showed worsened glucose tolerance under high-fat diet despite similar weight gain.
- Data support a BMAL1–HIF axis controlling circadian regulation of skeletal muscle glucose metabolism in obesity.
- Metabolite profiling indicates altered metabolic programs consistent with HIF-mediated reprogramming.
Clinical Implications
Chronotherapy and modulation of HIF signaling in muscle may improve glucose tolerance in obesity; aligning feeding/exercise with muscle clock function could be therapeutically beneficial.
Why It Matters
Revealing a BMAL1–HIF axis in skeletal muscle provides mechanistic insight into how circadian disruption worsens metabolic disease and suggests time- and pathway-targeted interventions.
Limitations
- Preclinical mouse study; human translational relevance needs confirmation.
- Abstracted data are incomplete; details of interventions and temporal dynamics are not provided here.
Future Directions
Test whether timed exercise/nutrition or HIF-targeted modulators improve glucose tolerance in obesity; validate BMAL1–HIF signatures in human muscle.
Study Information
- Study Type
- Basic/Mechanistic research
- Research Domain
- Pathophysiology/Prevention
- Evidence Level
- V - Mechanistic mouse model evidence linking circadian clock and metabolic pathways
- Study Design
- OTHER