Molecular Medicine of Leptin Regulation of Energy Metabolism and Its Medical Application

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Leptin is an important adipocytokine that acts directly on the hypothalamus, thereby regulating food intake and energy expenditure. Because leptin receptor is expressed not only in the hypothalamus but in a variety of peripheral tissues and leptin is capable of activating the JAK/STAT signaling pathway, suggesting that leptin works as a proinflammatory cytokine in peripheral target tissues.1)Leptin as an antidiabetic agent in insulin-deficient diabetes : We showed that after streptozotocin injection, both transgenic skinny mice overexpressing leptin and their non-transgenic littermates developed marked hyperglycemia as a result of severe hypoinsulinemia (termed diabetic TGM and diabetic WT, respectively). Diabetic TGM became normoglycemic, when treated with insulin at such doses that did not improve hyperglycemia in diabetic WT. This study suggests that leptin can be used as an adjunct of insulin therapy in insulin-deficient diabetes, thereby providing an insight into the therapeutic implication of leptin as an anti-diabetic agent.2)Pathonhvsioloizic role of leptin in ischemia-induced retinal neovascularization : Using the mouse retinopathy of prematurity model, we showed that leptin stimulates ischemia-induced retinal neovascularization possibly through the upregulation of endothelial VEGF. These observations suggest that leptin antagonism may offer a novel therapeutic strategy to prevent or treat diabetic retinopathy.3)Diagnostic role of leptin in as a biomarker of atherosclerosis : Given that leptin and adiponectin are important mediators linking adiposity and atherosclerosis in the adipovascular axis, we demonstrated that leptin/adiponectin ratio is strongly correlated with pulse-wave velocity, a direct measure of arterial stiffness. We, therefore, postulate that the ratio may serve as a potential atherogenic index in obese type 2 diabetic patients.