Metainflammation, Mitochondrial Dysfunction, and Organokine Crosstalk: A Central Axis Linking Metabolic Syndrome to Cardiovascular Diseases

Metabolic Syndrome (MetS) is a complex and multifactorial condition characterized by insulin resistance, visceral obesity, dyslipidemia, hypertension, and chronic low-grade inflammation, all of which contribute to increased cardiovascular risk. Central to its pathophysiology is metainflammation, a persistent inflammatory state closely linked to oxidative stress and mitochondrial dysfunction. This review aims to provide an integrated and updated overview of the interplay between metainflammation, oxidative stress, mitochondrial dysfunction, and organokine signaling in the development and progression of MetS and its cardiovascular complications. Current evidence indicates that mitochondrial dysfunction plays a pivotal role by promoting excessive production of reactive oxygen species (ROS), impairing ATP synthesis, and disrupting redox balance, thereby exacerbating insulin resistance and endothelial dysfunction. In parallel, dysregulated secretion of organokines—including adipokines, myokines, hepatokines, cardiokines, osteokines, and renokines—alters interorgan communication and amplifies pro-inflammatory and atherogenic pathways. Additionally, gut microbiota contributes to metabolic homeostasis through the production of short-chain fatty acids, whereas dysbiosis is associated with worsening metabolic parameters. Collectively, these interconnected mechanisms establish a self-perpetuating cycle that drives metabolic dysfunction and cardiovascular disease progression. This review highlights the central role of the metainflammation–mitochondrial dysfunction axis and emphasizes the importance of organokine-mediated crosstalk as a key regulator of systemic metabolism. Targeting these pathways may represent a promising strategy for the prevention and management of MetS and its associated complications.