Diet-Driven Inflammatory Signalling in Cardio-Metabolic Physiology: Molecular Pathways, Sex Differences, and Cardiovascular Consequences

Dietary patterns enriched in saturated fats and refined carbohydrates exert profound effects on metabolic and cardiovascular physiology by promoting chronic low-grade inflammation. Accumulating evidence indicates that diet-induced inflammatory signalling acts as a central integrator linking adipose tissue dysfunction, insulin resistance, endothelial impairment, and cardiovascular pathology. In this review, we synthesize current physiological insights into how pro-inflammatory diets activate innate immune pathways, including Toll-like receptor 4, nuclear factor-κB, mitogen-activated protein kinases, and the NLRP3 inflammasome thereby disrupting metabolic and vascular homeostasis. We highlight the coordinated roles of inflammatory cytokines, oxidative stress, lipid signalling, and immune–metabolic crosstalk in the pathogenesis of obesity, metabolic syndrome, hypertension, and atherosclerotic cardiovascular disease. Emerging evidence suggests that biological sex modifies inflammatory and metabolic responses to dietary excess through differences in adipose distribution, sex hormone signalling, immune regulation, and interactions with the gut microbiota. Together, these findings position diet-induced inflammation as a fundamental physiological mechanism linking nutrition to cardio-metabolic dysfunction and cardiovascular risk. Understanding these pathways provides a framework for developing targeted, physiology-informed dietary and therapeutic strategies aimed at reducing inflammation-driven cardiovascular disease.