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Updated: Jan 7, 2026

Isolation of Human Myoblasts, Assessment of Myogenic Differentiation, and Store-operated Calcium Entry Measurement
Published on: July 26, 2017
GABA induces myokine irisin release from skeletal muscle
Linling Fan1, Yijing Liao1, Zhihong Wang1
1Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, China.
Introduction:
γ-Aminobutyric acid (GABA), a classical neurotransmitter, also regulates skeletal muscle-an endocrine organ secreting irisin. This FNDC5-derived myokine induces white adipose tissue browning, augmenting thermogenesis and metabolic function.
Objectives:
This study investigated the effects of GABA on irisin secretion and its molecular mechanisms.
Methods:
In L6 myotubes, GABA activated GABAAR, causing membrane depolarization and calcium influx, which upregulated CREB phosphorylation and increased PGC-1α and FNDC5 expression, significantly elevating irisin secretion. In vivo, GABA treatment increased PGC-1α/FNDC5 expression in mouse skeletal muscle and raised serum irisin levels. Additionally, GABA-induced irisin promoted the browning of white adipose tissue by upregulating thermogenic genes and remodeling fat metabolism.
Conclusion:
These findings reveal a novel role for GABA in regulating myokine secretion and suggest its potential as a therapeutic target for metabolic diseases such as obesity and type 2 diabetes.
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