Acupuncture regulates neuroinflammation: microglial glucose metabolism reprogramming as a potential mediating...

Neuroinflammation is a common pathological feature shared by various central nervous system disorders. As the intrinsic immune cells of the brain, microglia exhibit activation states and functional phenotypes that are regulated by glucose metabolism reprogramming. Under physiological conditions, microglia primarily rely on oxidative phosphorylation to maintain energy homeostasis and immune surveillance. Upon pathological stimulation, however, microglia undergo metabolic reprogramming toward a pro-inflammatory mode dominated by glycolysis. This shift establishes a positive feedback loop between glycolysis and inflammation, which exacerbates neuronal damage. Acupuncture, as a classic non-pharmacological intervention, can suppress neuroinflammation by modulating microglial glucose metabolism reprogramming through multiple pathways. Recent studies have revealed that acupuncture can regulate glucose transporter expression and restore the activity and nuclear translocation of rate limiting enzymes such as hexokinase 2 and pyruvate kinase M2. It also modulates signaling axes including AMP activated protein kinase, mammalian target of rapamycin, and hypoxia inducible factor 1 alpha. These effects contribute to the phenotypic transition of microglia from a glycolysis dependent pro-inflammatory state to an oxidative phosphorylation dominated anti-inflammatory state. In addition, acupuncture exerts indirect anti-inflammatory effects by improving systemic glucose metabolism, optimizing cerebral blood flow, and regulating neurotransmitter balance, thereby reshaping the energy substrate composition of the brain microenvironment. This review systematically summarizes the important role of microglial glucose metabolism reprogramming in neuroinflammation and explores the potential molecular mechanisms through which acupuncture modulates this process. From a metabolic immune perspective, this work provides a new theoretical basis for acupuncture mediated alleviation of neuroinflammation.