While the impact of diet and exercise on adiponectin is controversial, the anti-inflammatory activity of this adipokine, able to inhibit NF-κB and TNF-α production in macrophages, is well established (Figure 1); consistent with these data, its serum concentrations are inversely related to obesity and chronic metabolic disorders, such as insulin resistance and diabetes. This evidence concerns the gene TNF and obesity due to melanocortin 4 receptor deficiency.