Fig. 3.

Both abdominal (visceral) fat and insulin resistance may contribute to cardiovascular disease in obesity. Visceral fat, in particular, contributes to endothelial dysfunction through the direct effect of adipokines, mainly adiponectin and TNF-α, which are secreted by fat tissue after macrophage recruitment (through monocyte chemoattractant protein-1, MCP-1). Indirect effects of TNF-α and IL-6 might influence inflammation (CRP) and endothelial dysfunction. Insulin resistance induced by cytokines (IL-6, TNF-α and adiponectin) NEFA and retinol-binding protein 4 (RBP-4) may induce oxidative stress and subsequent endothelial dysfunction (PAI-1 and ICAM-1). Fat accumulation, insulin resistance, liver-induced inflammation and dyslipidaemic features may all lead to the premature atherosclerotic process. (Nature 2008;454:463–9. Modified with permission).