Activation of brain lactate receptor GPR81 aggravates exercise-induced central fatigue

作者：Junxia Li, Yiming Xia, Honghao Xu, Renping Xiong, Yan Zhao, Ping Li, Tian Yang, Qingyuan Huang, Fabo Shan · 发表于：American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · 年份：2022 · DOI：10.1152/ajpregu.00094.2022 · 被引用次数：30 · 研究领域：Adipose Tissue and Metabolism、Cardiovascular and exercise physiology、Pharmacological Effects and Assays

Exercise-induced fatigue is a complex physiological phenomenon and is greatly influenced by central mechanisms in brain. As one of the most abundant circulating carbon metabolites, l-lactate in brain has been considered to be an important supplementary fuel during exercise; however, whether it plays a signaling role in fatigue remains largely obscure. In this study, our results initially revealed that brain l-lactate levels were increased after an exhaustive swimming session in several brain regions including motor cortex, hippocampus, and cerebellum. Then, we examined the specific role of brain lactate receptor, also known as hydroxycarboxylic acid receptor 1 (GPR81), in exercise-induced fatigue. We found that intracerebroventricular injection of either d-lactate (an enantiomer that could mediate activation of GPR81 as l-lactate) or a potent GPR81 agonist 3-chloro-5-hydroxybenzoic acid (CHBA), significantly decreased the swimming time to fatigue. After being subjected to the same weight-loaded swimming for 30 min, no obvious changes of blood lactate levels, gastrocnemius pAMPK/AMPK ratio, and glycogen contents were observed between intracerebroventricular CHBA-injected mice and vehicle-treated ones, which suggested a comparable degree of peripheral fatigue. Meanwhile, there were higher extracellular γ-aminobutyric acid (GABA) levels and lower extracellular glutamate levels and glutamate/GABA ratio in motor cortex of the intracerebroventricular CHBA-injected mice than that of...