The Role of Immunometabolic Dysregulation in Obesity-Associated Cardiovascular Risk: A Narrative Review

Resumen

Background: Obesity is a major global health problem and an established risk factor for cardiovascular disease (CVD). Beyond traditional risk factors, chronic low-grade inflammation and immune-cell metabolic dysfunction may provide a mechanistic link between obesity and vascular disease.

Objective: To synthesise current evidence on adipose tissue inflammation, monocyte and macrophage immunometabolic reprogramming, mitochondrial dysfunction, and the pathways connecting obesity with cardiovascular risk, while identifying emerging therapeutic targets.

Methods: A narrative review was conducted using PubMed, Scopus, Web of Science, and Google Scholar for studies published from 2000 to July 2026. Original human, animal, and in vitro studies addressing adipose tissue macrophages, immunometabolic reprogramming, inflammatory signalling, metabolic dysfunction, or cardiovascular outcomes were included and synthesised thematically.

Results: Obesity was consistently associated with adipose tissue macrophage recruitment and expansion, particularly through CCR2/CCL2 signalling, together with pro-inflammatory metabolic reprogramming characterised by increased glycolysis, altered fatty-acid oxidation, mitochondrial dysfunction, reactive oxygen species production, and activation of HIF-1α and NF-κB. The resulting release of TNF-α, IL-6, and IL-1β contributes to insulin resistance, endothelial dysfunction, hepatic steatosis, and atherosclerosis. Shared inflammatory and metabolic pathways were identified in obese adipose tissue and atherosclerotic lesions. However, a subgroup of individuals with obesity showed little adipose inflammation and relatively preserved vascular function, indicating that adipose tissue quality may be more informative than adiposity alone. Potential therapeutic targets include CCR2, AMPK, ANT2, SIRT3, mitochondrial reactive oxygen species, and dietary macronutrient composition.

Conclusion: Immunometabolic dysregulation appears to be a central mechanism linking obesity with cardiovascular disease. Strategies that restore immune-cell metabolism, preserve mitochondrial function, and reduce adipose tissue inflammation may complement conventional weight-management approaches, although further longitudinal and clinical studies are required.