# Ganoderic Acid A Enhances Glycometabolism in Mouse Gastrocnemius Muscle During Exercise‐Induced Fatigue via AMPK/PGC‐1α Pathway Activation

## TL;DR

Ganoderic Acid A improves exercise endurance and reduces fatigue in mice by boosting muscle energy metabolism through a key cellular pathway.

## Contribution

This study reveals a novel natural compound, Ganoderic Acid A, that combats exercise-induced fatigue via AMPK/PGC-1α/GLUT4 pathway activation.

## Key findings

- Ganoderic Acid A prolonged exhaustive running time and reduced fatigue markers in mice.
- The compound increased glycogen content and activated AMPK/PGC-1α/GLUT4 pathways in muscle.
- GAA improved energy metabolism and reduced muscle damage during exercise.

## Abstract

Exercise‐induced fatigue (EIF) is closely associated with impaired glycometabolism in skeletal muscle. This study investigated the protective effects of Ganoderic acid A (GAA) on glycometabolism in EIF mice and explored its underlying mechanisms. 60 KM mice were divided into five groups: a blank control (BC), a model control (MC), and three GAA‐treated groups (20, 40, and 60 mg/kg/d). After a 7‐week intervention, exhaustive treadmill tests and biochemical analyses were conducted to assess fatigue resistance, metabolic parameters, and molecular pathways. GAA administration significantly prolonged the exhaustive running time (p < 0.01), reduced serum levels of blood urea nitrogen (BUN), creatine kinase (CK), lactate dehydrogenase (LDH), and lactate (LD) (p < 0.05), and increased glycogen content in the liver and gastrocnemius muscle. Mechanistically, GAA increased AMPK phosphorylation, suggesting activation of the AMPK pathway, upregulated PGC‐1α and GLUT4 expression, and enhanced succinate dehydrogenase (SDH) and Ca2+‐Mg2+‐ATPase activities. The results demonstrate that GAA alleviates EIF by enhancing energy metabolism through the AMPK/PGC‐1α/GLUT4 pathway. These findings highlight GAA as a promising natural supplement for combating exercise‐induced fatigue by improving glycometabolism.

This study investigated the effects of GAA, an active ingredient in Ganoderma lucidum, on exercise‐induced fatigue. GAA effectively enhances exercise performance by improving endurance duration while simultaneously reducing metabolic byproducts and muscle fiber damage. Furthermore, GAA increases glycogen storage and enhances energy metabolism. Additionally, GAA stimulates AMPK and PGC1‐α, which induces GLUT4 expression, thereby improving glucose uptake and mitochondrial function. These findings suggest that GAA alleviates Exercise‐induced fatigue by improving energy metabolism via the AMPK/PGC‐1α/GLUT4 pathway, highlighting its potential as a natural anti‐fatigue supplement.