Levin Barry E
385 Tremont Avenue, VA Medical Center, Neurology Service (127C) E.Orange, NJ 07018-1095, United States.
Physiol Behav. 2005 Dec 15;86(5):633-9. doi: 10.1016/j.physbeh.2005.08.054. Epub 2005 Oct 17.
Obesity develops when energy intake exceeds expenditure. A constant neural, metabolic and hormonal "conversation" between the brain and periphery underlies the defense of a given level of adiposity. For the majority of humans, obesity becomes a permanent condition once it develops, possibly because of irreversible changes in the distributed network of specialized "metabolic sensing" neurons which regulate energy intake, expenditure and storage. Plasma leptin and insulin are catabolic hormones whose levels reflect the amount of adiposity and act as signal to metabolic sensing neurons. Obesity-prone individuals have an inborn reduction in their catabolic responses to glucose, leptin and insulin. These raised metabolic and hormonal sensing thresholds precede the development of obesity and predispose individuals to become and remain obese on energy dense diets. High fat diets exacerbate this problem by independently inhibiting central insulin and leptin signaling. In addition, intake of highly palatable diets overrides the homeostatic controls of ingestion because it is regulated by neural systems mediating reward and motivation. The genetic predisposition to become obese is accentuated in offspring of mothers who are obese or nutritionally deprived during gestation and/or lactation or by overfeeding during the early postnatal period. On the other hand, chronic stress and illness can both reduce adiposity, as does gastric bypass surgery. However, for chronic obesity treatment, both exercise and pharmacotherapy help but both must be continued chronically to provide sustained lowering of body weight in obese subjects. Given the permanent upward resetting of body weight set-point that occurs when genetically predisposed individuals become obese, identification of factors that prevent the development of obesity is likely to be the most successful means of ameliorating the current obesity epidemic.
当能量摄入超过消耗时，肥胖就会产生。大脑与外周之间持续的神经、代谢和激素“对话”是维持特定肥胖水平的基础。对于大多数人来说，肥胖一旦形成就会成为一种永久性状况，这可能是由于调节能量摄入、消耗和储存的特殊“代谢传感”神经元分布网络发生了不可逆转的变化。血浆瘦素和胰岛素是分解代谢激素，其水平反映肥胖程度，并作为信号传递给代谢传感神经元。易肥胖个体对葡萄糖、瘦素和胰岛素的分解代谢反应天生就有所降低。这些升高的代谢和激素传感阈值在肥胖发生之前就已出现，使个体在摄入能量密集型饮食时容易发胖并持续肥胖。高脂肪饮食通过独立抑制中枢胰岛素和瘦素信号来加剧这一问题。此外，摄入美味可口的食物会超越摄入的稳态控制，因为它受介导奖赏和动机的神经系统调节。在孕期和/或哺乳期肥胖或营养不足的母亲的后代，或者在出生后早期过度喂养的情况下，肥胖的遗传易感性会增强。另一方面，慢性应激和疾病都可以减轻肥胖，胃旁路手术也有同样的效果。然而，对于慢性肥胖的治疗，运动和药物治疗都有帮助，但两者都必须长期持续进行，才能使肥胖受试者的体重持续下降。鉴于遗传易感性个体肥胖时体重设定点会永久性上调，识别预防肥胖发生的因素可能是改善当前肥胖流行状况最成功的方法。
