The lactate-GPR81-PKA axis regulates exercise-induced central fatigue in male mice

American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 2026 Open access

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Authors: J. Li, Miaomiao Tan, Zegang Hu, S. Zhou, Zhengbi Liu, C. Wang, P. Li, Fabo Shan
DOI: 10.1152/ajpregu.00103.2025
Cited by: 1
References: 54

Abstract

Exercise-induced fatigue is regulated by factors derived from the central nervous system (CNS), including neurotransmitters and metabolic signals. However, the underlying mechanisms remain largely obscure. Here, we demonstrate that lactate activates GPR81 in the motor cortex to inhibit PKA phosphorylation, thereby contributing to central fatigue during exercise. These findings reveal a vital role of lactate-GPR81-PKA axis in the motor cortex during exercise and provide a potential target for alleviating exercise-induced central fatigue.

Fields of Study & Subjects

Sports Performance and Training Genetics and Physical Performance Receptor Mechanisms and Signaling

Publication details

Journal / source
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
Publisher
American Physiological Society
Volume
330
Issue
2
Pages
R126–R135
Publication date
8 January 2026
Language
EN