Obesity represents the single most important risk factor for early disability and death in developed societies, and the incidence of obesity remains at staggering levels. CNS systems that modulate energy intake and expenditure in response to changes in body energy stores serve to maintain constant body adiposity; the adipocyte-derived hormone leptin and its receptor (LEPR) represent crucial regulators of these systems. As in the case of insulin resistance, a variety of mechanisms (including feedback inhibition, inflammation, gliosis and endoplasmic reticulum stress) have been proposed to interfere with leptin action and impede the systems that control body energy homeostasis to promote or maintain obesity, although the relative importance and contribution of each of these remain unclear. However, LEPR signalling may be increased (rather than impaired) in common obesity, suggesting that any obesity-associated defects in leptin action must result from lesions somewhere other than the initial LEPR signal. It is also possible that increased LEPR signalling could mediate some of the obesity-associated changes in hypothalamic function.

在发达社会中，肥胖是导致早期残疾和死亡的最重要的单一危险因素，肥胖的发生率仍处于惊人的水平。中枢神经系统可根据人体能量储存的变化调节能量的摄入和消耗，以维持恒定的身体脂肪。脂肪细胞源性激素瘦素及其受体（LEPR）代表了这些系统的关键调节因子。与胰岛素抵抗一样，已经提出了多种机制（包括反馈抑制，炎症，神经胶质细胞增生和内质网应激）来干扰瘦素作用并阻碍控制身体能量稳态以促进或维持肥胖的系统。这些因素的相对重要性和贡献仍不清楚。然而，在普通肥胖症中，LEPR信号传导可能增加（而不是受损），这表明与肥胖症相关的瘦素作用缺陷必定是由最初LEPR信号以外的其他部位引起的。LEPR信号转导增加也可能介导一些与肥胖相关的下丘脑功能变化。