Adipose-derived mesenchymal stromal cell-microenvironment interaction network in metabolic syndrome: ADMSC injury response, adaptive regulation, and regenerative potential

Metabolic syndrome (MetS) is a complex metabolic disorder characterized by insulin resistance, central obesity, dyslipidemia, hypertension, and chronic inflammation, which collectively increase the risk of type 2 diabetes mellitus, cardiovascular disease, and metabolic dysfunction-associated steatotic liver disease. Although adipose-derived mesenchymal stromal cells (ADMSCs) have shown promising therapeutic potential in preclinical studies, their efficacy is substantially influenced by the diseased local microenvironment. Accumulating evidence indicates that ADMSCs exert multi-target therapeutic effects in MetS by alleviating insulin resistance, modulating inflammation, restoring mitochondrial and redox homeostasis, regulating lipid metabolism, and protecting vascular and metabolic organ function. However, the pathological state associated with MetS, characterized by chronic inflammation, oxidative stress, and metabolic imbalance, can reciprocally impair ADMSC function and limit their therapeutic efficacy. In this review, we summarize the current mechanistic understanding of ADMSC-based therapy for MetS and highlight the bidirectional interaction between ADMSCs and the local microenvironment network, discussing how exosome-based and microenvironment-oriented strategies may support the development of more precise and effective regenerative interventions for metabolic disease.