Circadian rhythm disruption linked to skeletal muscle dysfunction in the Mexican Cavefish

Luke Olsen1, Jaya Krishnan2, Charles Banks2

  • 1Stowers Institute for Medical Research, Kansas City, MO 64110, USA; Department of Cell Biology & Physiology, University of Kansas Medical Center, Kansas City, KS 66103, USA.

Current Biology : CB
|April 11, 2023
PubMed

Insights

Peripheral circadian clocks regulate skeletal muscle function. In Mexican cavefish, disrupted muscle clock function leads to gene rhythm disruption and impaired protein breakdown, potentially explaining muscle weakness.

Area of Science:

  • * Chronobiology
  • * Molecular Biology
  • * Physiology

Background:

  • * Circadian clocks in peripheral tissues, particularly skeletal muscle, are crucial for normal physiological function.
  • * Disruptions to skeletal muscle circadian clocks are linked to conditions like insulin resistance and muscle weakness.
  • * Mexican cavefish (Astyanax mexicanus) possess a disrupted central circadian clock, prompting investigation into their peripheral clock mechanisms.

Purpose of the Study:

  • * To investigate the functional status of the circadian clock in the skeletal muscle of Mexican cavefish.
  • * To determine if alterations in peripheral clocks contribute to observed muscle phenotypes in cavefish.
  • * To identify specific genes and molecular pathways affected by clock disruption in cavefish skeletal muscle.

Main Methods:

  • * Analysis of gene expression rhythmicity in skeletal muscle tissue of Mexican cavefish.
  • * Assessment of protein catabolism patterns during nocturnal periods.
  • * Comparative analysis of gene functions related to human metabolic disorders.

Main Results:

  • * Demonstrated a significant loss of circadian clock function in the skeletal muscle of Mexican cavefish.
  • * Observed reduced rhythmicity in a large number of genes within the skeletal muscle.
  • * Identified disrupted nocturnal protein catabolism and identified genes linked to human metabolic dysfunction.

Conclusions:

  • * The Mexican cavefish exhibits impaired skeletal muscle circadian clock function, independent of central clock disruption.
  • * This peripheral clock dysfunction contributes to molecular and physiological alterations in skeletal muscle.
  • * The identified genes offer insights into the molecular basis of muscle weakness and metabolic dysfunction in cavefish and potentially humans.

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