Department of Psychiatry and Biobehavioral Sciences and Semel Institute, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California 90024, USA.
J Clin Endocrinol Metab. 2011 Aug;96(8):E1212-20. doi: 10.1210/jc.2011-0314. Epub 2011 May 25.
Leptin affects neurogenesis, neuronal growth, and viability. We previously reported that leptin supplementation increased gray matter (GM) concentration in the anterior cingulate gyrus (ACG), cerebellum, and inferior parietal lobule, areas that are also involved in food intake.
The aim of this study was to report the changes in brain structure at different states of leptin supplementation.
We conducted a nonrandomized trial.
We studied three adults with congenital leptin deficiency due to a mutation in the leptin gene.
Patients received treatment with recombinant methionyl human leptin, with annual 11- to 36-d periods of treatment withholding followed by treatment restoration over 3 yr.
GM concentration (by voxel-based morphometry analysis of magnetic resonance scans) was correlated with body mass index (BMI) and leptin supplementation.
Annually withholding leptin supplementation for several weeks increased BMI and reversed the original effects of leptin in the cerebellum and ACG. The changes in the ACG were consistent with an indirect effect of leptin mediated through increased BMI. In the cerebellum, where leptin receptors are most dense, GM changes appeared to be direct effects of leptin. Leptin restoration did not lead to recovery of GM in the short term but did lead to an unexpected GM increase in the posterior half of the left thalamus, particularly the pulvinar nucleus.
These findings provide the first in vivo evidence of remarkably plastic, reversible, and regionally specific effects of leptin on human brain morphology. They suggest that leptin may have therapeutic value in modulating plasticity-dependent brain functions.
瘦素会影响神经发生、神经元生长和活力。我们之前曾报道过，瘦素补充可以增加扣带回前回（ACG）、小脑和下顶叶的灰质（GM）浓度，这些区域也与食物摄入有关。
本研究旨在报告不同瘦素补充状态下大脑结构的变化。
我们进行了一项非随机试验。
我们研究了三名因瘦素基因突变而患有先天性瘦素缺乏症的成年人。
患者接受重组甲硫氨酸人瘦素治疗，每年有 11 至 36 天的治疗停药期，随后在 3 年内恢复治疗。
GM 浓度（通过磁共振扫描的基于体素的形态计量学分析）与体重指数（BMI）和瘦素补充相关。
每年停药数周会增加 BMI，并逆转瘦素对小脑和 ACG 的原始作用。ACG 的变化与瘦素通过增加 BMI 介导的间接作用一致。在小脑，瘦素受体最密集，GM 的变化似乎是瘦素的直接作用。短期内瘦素的恢复并没有导致 GM 的恢复，但确实导致左丘脑后半部分（特别是丘脑枕核）的 GM 意外增加。
这些发现为瘦素对人类大脑形态的显著可塑、可逆和区域特异性影响提供了首个体内证据。它们表明，瘦素在调节依赖可塑性的大脑功能方面可能具有治疗价值。
