Short-Term Plasticity of Gray Matter Associated with Leptin Deficiency and Replacement

Department of Psychiatry and Biobehavioral Sciences and Semel Institute, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California 90024, USA.
The Journal of Clinical Endocrinology and Metabolism (Impact Factor: 6.21). 05/2011; 96(8):E1212-20. DOI: 10.1210/jc.2011-0314
Source: PubMed


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. Intervention: 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.

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Available from: Gilberto Paz-Filho, Feb 20, 2014
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    • "There is increasing evidence that the cerebellum plays an important role in feeding and eating behaviours, and it might in fact be a 'central node' for regulation of feeding intake, with connections from/to the hypothalamus (Mahler, Guastavino, Jacquart, & Strazielle, 1993; Zhu & Wang, 2008). Posterior cerebellum activation has been shown when showing images of desirable food (Berman et al., 2013), and posterior cerebellum grey matter plasticity has been shown in response to leptin (London et al., 2011). Given that the cerebellum also plays a role in cognitive function, emotion regulation (Schmahmann, 2010), the role of the cerebellum in ED requires further exploration. "
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    • "Similarly, in three congenitally leptin deficient human adults, leptin treatment has been shown to increase gray matter volume in cerebellum, inferior parietal, and anterior cingulate cortices [113]. Furthermore, in these same patients, small reductions in gray matter volume were detected in these same areas when leptin treatment was discontinued [114]. In healthy adults, plasma leptin levels have been associated with total brain volume, independent of body size [115] [116] [117]. "
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