van de Sande-Lee Simone, Velloso Licio A
Laboratório de Sinalização Celular, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (FCM-Unicamp), Campinas, SP, Brasil.
Arq Bras Endocrinol Metabol. 2012 Aug;56(6):341-50. doi: 10.1590/s0004-27302012000600001.
Obesity, defined as abnormal or excessive fat accumulation that may impair life quality, is one of the major public health problems worldwide. It results from an imbalance between food intake and energy expenditure. The control of energy balance in animals and humans is performed by the central nervous system (CNS) by means of neuroendocrine connections, in which circulating peripheral hormones, such as leptin and insulin, provide signals to specialized neurons of the hypothalamus reflecting body fat stores, and induce appropriate responses to maintain the stability of these stores. The majority of obesity cases are associated with central resistance to both leptin and insulin actions. In experimental animals, high-fat diets can induce an inflammatory process in the hypothalamus, which impairs leptin and insulin intracellular signaling pathways, and results in hyperphagia, decreased energy expenditure and, ultimately, obesity. Recent evidence obtained from neuroimaging studies and assessment of inflammatory markers in the cerebrospinal fluid of obese subjects suggests that similar alterations may be also present in humans. In this review, we briefly present the mechanisms involved with the loss of homeostatic control of energy balance in animal models of obesity, and the current evidence of hypothalamic dysfunction in obese humans.
肥胖被定义为可能损害生活质量的异常或过度脂肪堆积，是全球主要的公共卫生问题之一。它是由食物摄入与能量消耗之间的不平衡导致的。动物和人类的能量平衡控制由中枢神经系统（CNS）通过神经内分泌联系来执行，在这种联系中，循环的外周激素，如瘦素和胰岛素，向反映身体脂肪储存的下丘脑专门神经元提供信号，并诱导适当反应以维持这些储存的稳定性。大多数肥胖病例与对瘦素和胰岛素作用的中枢抵抗有关。在实验动物中，高脂饮食可在下丘脑诱导炎症过程，这会损害瘦素和胰岛素的细胞内信号通路，并导致食欲亢进、能量消耗减少，最终导致肥胖。最近从神经影像学研究以及肥胖受试者脑脊液中炎症标志物评估获得的证据表明，人类可能也存在类似的改变。在这篇综述中，我们简要介绍肥胖动物模型中能量平衡稳态控制丧失所涉及的机制，以及肥胖人类下丘脑功能障碍的当前证据。
