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

Figures

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  Figure 1. Central axis of MetS: metainflammation, oxidative stress, and mitochondrial dysfunction. Schematic representation of the central pathophysiological triad underlying Metabolic Syndrome. Metainflammation, oxidative stress, and mitochondrial dysfunction interact bidirectionally, forming a vicious cycle that perpetuates insulin resistance, endothelial dysfunction, and tissue injury. These interconnected processes contribute to the development and progression of cardiovascular disease and other metabolic complications. Each element of the triad amplifies the others, exacerbating systemic inflammation and impairing cellular energy homeostasis; ROS, Reactive Oxygen Species. Figure prepared with Canva.com.

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  Figure 2. Overview of mitochondrial alterations observed in MetS. Electron leakage from the respiratory chain leads to excessive production of ROS, reduced ATP synthesis, and mtDNA release. These events contribute to redox imbalance, activation of apoptotic pathways, and stimulation of the NLRP3 inflammasome, triggering pro-inflammatory responses. Mitochondrial dysfunction is a central factor in insulin resistance, oxidative stress, and cellular damage in metabolic tissues, further contributing to the development of cardiovascular and metabolic diseases. ROS: Reactive Oxygen Species. Figure prepared with Canva.com.

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  Figure 3. Gut microbiota, SCFAs, and their impact on metabolic health. The role of the gut microbiota in regulating metabolic health through the production of SCFAs (acetate, propionate, and butyrate). SCFAs improve insulin sensitivity, lipids, and blood pressure; reduce BMI, modulate appetite, and reduce systemic inflammation, oxidative stress, and mitochondrial dysfunction. Dysbiosis and decreased SCFA production contribute to the pathophysiology of MetS. BMI: body mass index; SCFAs: short-chain fatty acids. Figure prepared with Canva.com and improved by GPT.com.

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  Figure 4. Interorgan crosstalk in metabolic syndrome (MetS). Interorgan communication mediated by organokines, bioactive molecules secreted by metabolically active organs, including skeletal muscle (myokines), liver (hepatokines), adipose tissue (adipokines), heart (cardiokines), bone (osteokines), and kidney (renokines). Through endocrine, paracrine, and autocrine signaling, these organokines regulate inflammation, oxidative stress, mitochondrial function, insulin sensitivity, lipid metabolism, and vascular homeostasis. In MetS, chronic low-grade inflammation and metabolic stress disrupt organokine secretion, leading to impaired interorgan communication that contributes to insulin resistance, dyslipidemia, endothelial dysfunction, and the progression of cardiometabolic complications. Abbreviations: MetS, metabolic syndrome; FGF21, fibroblast growth factor 21; ANGPTL8, angiopoietin-like protein 8; BDNF, brain-derived neurotrophic factor; IL-6, interleukin-6; ANP, atrial natriuretic peptide; BNP, B-type natriuretic peptide; GDF15, growth differentiation factor 15; FGF23, fibroblast growth factor 23; ROS, reactive oxygen species; NAFLD, non-alcoholic fatty liver disease. Figure prepared with…

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  Figure 5. Illustration of interorgan communication mediated by organokines, bioactive molecules secreted by various organs involved in metabolic regulation. Skeletal muscle (myokines), liver (hepatokines), adipose tissue (adipokines), heart (cardiokines), bone (osteokines), kidney (renokines), and intestine (enterokines) release signaling molecules such as irisin, FGF-21, adiponectin, ANP, osteocalcin, erythropoietin, and GLP-1. These organokines modulate inflammation, insulin sensitivity, lipid metabolism, and vascular function. Dysregulation of this interaction plays a crucial role in the pathogenesis of MetS and its cardiometabolic complications. Abbreviations: ANP: atrial natriuretic peptide; GLP-1: Glucagon-like peptide 1; FGF-21: fibroblast growth factor 21. Figure prepared with Canva.com and improved by GPT.com.