Chrono overexpression blunts exercise-induced improvement in muscular glucose metabolism by inhibiting the BMAL1 transcriptional activity in high-fat diet-fed mice - PubMed
3 hours ago
- #Chrono BMAL1 pathway
- #Glucose intolerance
- #Exercise metabolism
- Overexpression of the Chrono protein in skeletal muscle blunts the beneficial effects of aerobic exercise on glucose metabolism in mice fed a high-fat diet.
- Chrono overexpression inhibits the dissociation of CHRONO from BMAL1, preventing the normal transcriptional activation by BMAL1 that exercise typically induces.
- Exercise in Chrono-overexpressing mice fails to improve systemic insulin sensitivity, adipose mass, and dyslipidemia despite increases in signaling markers like p-TBC1D1Ser237 and GLUT4 expression.
- The lack of CHRONO-BMAL1 dissociation hinders GLUT4 membrane trafficking and the upregulation of key glycolytic and glycogen metabolic genes in muscle, essential for exercise-induced metabolic adaptations.
- This study establishes that CHRONO-BMAL1 dissociation is a required step for exercise to confer metabolic benefits against high-fat diet-induced dysfunction in skeletal muscle.