As AT is a storage depot for fat, physiologically low AT levels lead to elevated circulating concentrations of TAG and FFAs and development of IR.181, 182 Healthy AT is also required for proper secretion and the physiological balance of adipokines like adopinectin and leptin, which sensitize cells to insulin.183, 184 Leptin replacement therapy is now an approved treatment for patients with lipodystrophy, and significantly attenuates IR in those patients.185 Functional AT in proportion to body size is thus essential for normal insulin sensitivity and whole-body metabolism. Here, LEP is linked to lipodystrophy.