TNF and obesity due to melanocortin 4 receptor deficiency: However, in contrast to these findings in macrophages, treatment of adipocytes with S1P has been shown to have pro-inflammatory/pro-thrombotic actions, leading to increased gene expression of plasminogen activator inhibitor-1, TNF-α, interleukin-6, and keratinocyte-derived chemokine [12], thus adding further complexity to its role in obesity and metabolic dysfunction.