Recent experimental and clinical evidence has suggested a synergistic causal role among adipose tissue hypertrophy, dyslipidemia, and systemic inflammation in the development and instability of the atherosclerotic plaque. Here, we summarize some of the most recent findings regarding the role of white adipose tissue hypertrophy in the development of dyslipidemia and chronic low-grade systemic inflammation. We also review the contribution of dyslipidemia in releasing free-fatty acids, cholesterol, and oxidized low-density lipoproteins as metabolic ligands able to trigger inflammatory signal pathways in macrophages via pattern recognition receptor (PRR) activation. Finally, we discuss the possible mechanisms through which dyslipidemia-related metabolic ligands and chronic low-grade systemic inflammation are capable of inducing macrophage activation, which in turn is involved in mediating instability and rupture of the atherosclerotic plaque. A better understanding of the inflammatory mechanisms contributing to atherosclerosis may help to identify potential molecular targets to decrease the cardiovascular risk in patients by using anti-inflammatory therapies and PRR blockers.
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