INS and obesity due to melanocortin 4 receptor deficiency: Interestingly, leptin is known to mediate the effects of lipopolysaccharide (LPS) induced anorexia and fever [98], but central leptin (and insulin) resistance is a common finding in obesity and could be related to leptin itself via effects on phosphatidylinositol 3-kinase (PI3K) and phosphodiesterase 3B (PDE3B) activities and reduction in cyclic AMP (cAMP) [99] and/or the pro-inflammatory effects of a high fat diet [100].