Exploring Mechanism of Glucose Metabolic Reprogramming-driven Macrophage Polarization in Regulating Metabolic Syndrome Based on Theory of "Spleen Qi Dispersing Essence"
10.13422/j.cnki.syfjx.20260662
- VernacularTitle:基于“脾气散精”理论探讨糖代谢重编程驱动巨噬细胞极化调控代谢综合征的机制
- Author:
Jinshun YOU
1
;
Shijie QIAO
1
;
Linzhen LI
1
;
Lingfang ZHENG
1
;
Shujie XIA
1
Author Information
1. School of Traditional Chinese Medicine(TCM),Fujian University of TCM,Fuzhou 350122,China
- Publication Type:Journal Article
- Keywords:
metabolic syndrome;
phlegm-dampness;
spleen Qi dispersing essence;
macrophages;
metabolic reprogramming
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(20):221-229
- CountryChina
- Language:Chinese
-
Abstract:
Metabolic syndrome (MS) is a clinical syndrome characterized by obesity, insulin resistance, and dyslipidemia, and chronic inflammation is closely associated with its pathogenesis. The imbalance between pro-inflammatory and anti-inflammatory macrophage polarization, as one of the core pathological mechanisms of chronic inflammation, is a crucial driver of MS progression. According to Essential Questions in Yellow Emperor's Inner Canon: Distinctive Theory on Meridians and Diseased Pulses, "the spleen Qi dispersing essence... along all the meridians and collaterals". When the spleen fails in transportation and transformation, the distribution of refined essence becomes disordered, leading to internal accumulation of phlegm-dampness, forming a dynamic pathological state of "root deficiency with branch excess". Accordingly, the core traditional Chinese medicine (TCM) pathogenesis of MS is closely related to "spleen failing in transportation and transformation coupled with the internal accumulation of phlegm-dampness"; however, its modern biological basis remains elusive. Therefore, based on the theory of "spleen Qi dispersing essence" and recent advances in immunometabolism, this paper explored the modern scientific connotation of the TCM pathogenesis of MS from the perspective of macrophage polarization driven by glucose metabolic reprogramming. Through theoretical analysis and literature integration, it was proposed that mitochondrial oxidative phosphorylation participates in the energy metabolism process of "spleen Qi dispersing essence". The dysfunction of the spleen's transportation and transformation prompts macrophage metabolism to shift toward glycolysis, resulting in the accumulation of lactate and succinate, which represents the microscopic manifestation of "refined essence deviating from proper transformation" and can be defined as "microscopic phlegm-dampness". These metabolites subsequently drive M1 macrophage polarization via the hypoxia-inducible factor-1α (HIF-1α)/nuclear factor-κB (NF-κB) signaling pathway, triggering the release of pro-inflammatory cytokines and inducing systemic chronic low-grade inflammation, ultimately manifesting as insulin resistance, lipid metabolic disorders, and other core components of MS, thus achieving immune amplification from local "microscopic phlegm-dampness" to systemic "internal accumulation of phlegm-dampness". Therefore, macrophage polarization driven by glucose metabolic reprogramming constitutes an important biological link connecting the TCM concept of "spleen failing to disperse essence" with the pathology of MS. Furthermore, this paper reviewed the potential mechanisms by which TCM herbal formulas and their monomeric components that "restore spleen transportation and resolve phlegm-dampness" ameliorate MS by modulating macrophage metabolic remodeling, thereby providing novel biological connotations for the modern interpretation of the theory of "spleen Qi dispersing essence". Future research should integrate multi-omics technologies with disease-syndrome animal models to elucidate the regulatory network of formulas that "restore spleen transportation and resolve phlegm-dampness". Additionally, the feasibility of utilizing macrophage metabolic phenotypes as objective diagnostic biomarkers for the phlegm-dampness syndrome in MS warrants further investigation.