Department of Nutrition, Food Sciences and Physiology, University of Navarra, C/Irunlarrea 1, 31008 Pamplona, Spain.
Department of Nutrition, Food Sciences and Physiology, University of Navarra, C/Irunlarrea 1, 31008 Pamplona, Spain; CIBER Fisiopatología de la Obesidad y la Nutrición (CIBERobn), Instituto de Salud Carlos III, 28029 Madrid, Spain.
Metabolism. 2015 Jan;64(1):35-46. doi: 10.1016/j.metabol.2014.10.015. Epub 2014 Oct 23.
Obesity is a chronic disease that represents one of the most serious global health burdens associated to an excess of body fat resulting from an imbalance between energy intake and expenditure, which is regulated by environmental and genetic interactions. The adipose-derived hormone leptin acts via a specific receptor in the brain to regulate energy balance and body weight, although this protein can also elicit a myriad of actions in peripheral tissues. Obese individuals, rather than be leptin deficient, have in most cases, high levels of circulating leptin. The failure of these high levels to control body weight suggests the presence of a resistance process to the hormone that could be partly responsible of disturbances on body weight regulation. Furthermore, leptin resistance can impair physiological peripheral functions of leptin such as lipid and carbohydrate metabolism and nutrient intestinal utilization. The present document summarizes those findings regarding leptin resistance development and the role of this hormone in the development and maintenance of an obese state. Thus, we focused on the effect of the impaired leptin action on adipose tissue, liver, skeletal muscle and intestinal function and the accompanying relationships with diet-induced obesity. The involvement of some inflammatory mediators implicated in the development of obesity and their roles in leptin resistance development are also discussed.
肥胖是一种慢性疾病，是由于能量摄入和消耗之间失衡导致体脂肪过多而引起的，与全球健康负担最严重的问题之一有关，这种失衡受到环境和遗传相互作用的调节。脂肪组织分泌的激素瘦素通过大脑中的特定受体发挥作用，以调节能量平衡和体重，尽管这种蛋白质也可以在外周组织中引起多种作用。肥胖个体，而不是瘦素缺乏，在大多数情况下，循环瘦素水平较高。这些高水平未能控制体重表明存在对激素的抵抗过程，这可能是导致体重调节紊乱的部分原因。此外，瘦素抵抗会损害瘦素的生理外周功能，如脂质和碳水化合物代谢以及营养物质的肠道利用。本文总结了关于瘦素抵抗发展的这些发现，以及该激素在肥胖状态的发展和维持中的作用。因此，我们重点研究了受损的瘦素作用对脂肪组织、肝脏、骨骼肌和肠道功能的影响，以及伴随的与饮食诱导肥胖的关系。还讨论了一些与肥胖发展有关的炎症介质的参与及其在瘦素抵抗发展中的作用。
