Programmed cell death in metabolic syndrome: From molecular mechanisms to therapeutic strategies (Review)

Metabolic syndrome (MetS) is a clinical syndrome primarily characterized by insulin resistance, integrating central obesity, hyperglycemia, hypertension and dyslipidemia. It is associated with increased risks of type 2 diabetes mellitus, non‑alcoholic fatty liver disease and atherosclerosis. Due to its high prevalence, complex pathogenesis and lack of effective treatments, MetS has become a notable global health issue. Current therapeutic approaches mainly emphasize weight reduction through caloric restriction and increased physical activity, or pharmacological interventions to improve lipid profiles, blood pressure and blood glucose; however, their efficacy remains suboptimal. Growing evidence indicates that programmed cell death (PCD), as a key driver of inflammation, serves a crucial role in the development and progression of MetS. The present review provides a comprehensive overview of recent advances in the understanding of how established and emerging forms of PCD contribute to MetS pathogenesis, including apoptosis, pyroptosis, autophagy, ferroptosis, necroptosis, PANoptosis and disulfidptosis. Particular emphasis is placed on their molecular mechanisms, tissue‑specific functions, regulatory crosstalk and therapeutic potential. Additionally, the present review discusses novel regulatory approaches and potential therapeutic strategies based on PCD network intervention, offering theoretical foundations and directions for developing innovative therapies to prevent and treat MetS and its complications.