Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Ann N Y Acad Sci. 2010 Nov;1211:51-65. doi: 10.1111/j.1749-6632.2010.05810.x.
Anorexia nervosa (AN), a disorder characterized by the refusal to sustain a healthy weight, has the highest mortality of any psychiatric disorder. This review presents a model of AN that ties together advances in our understanding of how leptin, serotonin, and hypogonadism are brought about in AN and how they influence bone mass. Serotonin (5-hydroxytryptamine) is a key regulator of satiety and mood. The primary disturbance in AN results from alterations in serotonin signaling. AN patients suffer from serotonergic hyperactivity of Htr1a-dependent pathways that causes dysphoric mood and promotes restrictive behavior. By limiting carbohydrate ingestion, anorexics decrease their serotonin levels. Reduced serotonergic signaling in turn suppresses appetite through Htr1a/2b, decreases dysphoric mood through Htr1a/2a, and activates the sympathetic nervous system (SNS) through Htr2c receptors in the ventromedial hypothalamus. Activation of the SNS decreases bone mass through β2-adrenergic signaling in osteoblasts. Additional topics reviewed here include osteoblastic feedback of metabolism in anorexia, mechanisms whereby dietary changes exacerbate bone loss, the role of caloric restriction and Sirt1 in bone metabolism, hypothalamic hypogonadism's effects on bone mass, and potential treatments.
神经性厌食症（AN），一种以拒绝维持健康体重为特征的疾病，其死亡率高于任何精神疾病。本综述提出了一个 AN 模型，将我们对瘦素、血清素和性腺功能减退症在 AN 中是如何产生的以及它们如何影响骨量的理解联系起来。血清素（5-羟色胺）是饱腹感和情绪的主要调节剂。AN 患者主要的紊乱是由于血清素信号的改变。AN 患者患有 Htr1a 依赖性途径的血清素能过度活跃，导致情绪不佳和促进限制行为。通过限制碳水化合物的摄入，厌食症患者会降低他们的血清素水平。反过来，减少的血清素信号通过 Htr1a/2b 抑制食欲，通过 Htr1a/2a 降低情绪不佳，并通过腹内侧下丘脑的 Htr2c 受体激活交感神经系统（SNS）。SNS 的激活通过成骨细胞中的β2-肾上腺素能信号降低骨量。本文还讨论了厌食症中代谢的成骨细胞反馈、饮食变化如何加剧骨丢失、热量限制和 Sirt1 在骨代谢中的作用、下丘脑性腺功能减退对骨量的影响以及潜在的治疗方法。
