LEP and obesity due to melanocortin 4 receptor deficiency: In addition to chronic inflammation, adipocyte overloading and lipotoxicity inobesity has a major impact on adipose tissue function, resulting in an adverseadipokine profile (Fig. 1).In particular, a reduction in adiponectin production is thought to be a majorpathogenic factor in metabolic disease.17,18 Conversely, levels of theproinflammatory adipokine leptin are increased in obesity.19,20