Prompt Description

Lactic acid exerts diverse physiological functions by activating three main signaling pathways via the GPR81 receptor. In the cAMP-AC pathway, upon binding to GPR81, lactic acid inhibits adenylyl cyclase through Gi protein, reducing cAMP levels and PKA activity. This process inhibits lipolysis and promotes triglyceride storage in adipose tissue, reduces CREB phosphorylation and increases intramuscular fat accumulation in muscle tissue, and decreases neuronal excitability to trigger an energy-saving mode in brain tissue. In the ERK1/2 pathway, the lactic acid-GPR81 signal activates the Ras-Raf-MEK-ERK cascade through the Giβγ subunit, promoting skeletal muscle hypertrophy and enhanced mitochondrial function, increasing ATP production and oxidative phosphorylation capacity, while also regulating bone metabolism by promoting osteoblast differentiation and inhibiting osteoclasts. In the β-arrestin pathway, lactic acid activates GPR81 and recruits β-arrestin2, which inhibits the TLR4/NLRP3 inflammasome to exert anti-inflammatory effects and reduce IL-1β production, and promotes STAT1/2 dephosphorylation to participate in tumor immune escape. These three pathways collectively constitute the GPR81-mediated lactic acid signaling network, regulating various physiological processes such as metabolic balance, exercise adaptation, and immune responses.