title: Short-term plasticity of gray matter associated with leptin deficiency and replacement.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  The aim of this study was to report the changes in brain structure at different states of leptin supplementation.
  
  
  METHODS
  We conducted a nonrandomized trial.
  
  
  METHODS
  We studied three adults with congenital leptin deficiency due to a mutation in the leptin gene.
  
  
  METHODS
  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.
  
  
  METHODS
  GM concentration (by voxel-based morphometry analysis of magnetic resonance scans) was correlated with body mass index (BMI) and leptin supplementation.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Psychiatry and Biobehavioral Sciences and Semel Institute, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California 90024, USA. elondon@mednet.ucla.edu
authors: Edythe D
authors: ED
authors: London
authors: Steven M
authors: SM
authors: Berman
authors: Shruthi
authors: S
authors: Chakrapani
authors: Tuncay
authors: T
authors: Delibasi
authors: John
authors: J
authors: Monterosso
authors: H Kutlu
authors: HK
authors: Erol
authors: Gilberto
authors: G
authors: Paz-Filho
authors: Ma-Li
authors: ML
authors: Wong
authors: Julio
authors: J
authors: Licinio
references: Obesity (Silver Spring). 2008 Jan;16(1):119-24
references: 18223623
references: Int J Clin Pract. 2010 Dec;64(13):1808-12
references: 21070531
references: Cell Metab. 2008 May;7(5):400-9
references: 18460331
references: Biol Psychiatry. 2009 Jun 1;65(11):992-4
references: 19026409
references: J Neurosci. 2010 Feb 3;30(5):1894-904
references: 20130198
references: Nat Rev Neurosci. 2007 Jun;8(6):481-8
references: 17514200
references: Biol Psychiatry. 2003 Nov 1;54(9):934-42
references: 14573322
references: Am J Clin Nutr. 2009 Mar;89(3):980S-984S
references: 19211814
references: Neurology. 2004 Nov 23;63(10):1876-81
references: 15557505
references: Neurosci Lett. 2007 Feb 2;412(3):248-53
references: 17123711
references: Proc Natl Acad Sci U S A. 2007 Nov 13;104(46):18276-9
references: 17986612
references: Nature. 2004 Jan 22;427(6972):311-2
references: 14737157
references: JAMA. 2009 Dec 16;302(23):2565-72
references: 20009056
references: Neuroimage. 2005 Nov 15;28(3):544-52
references: 16085427
references: J Clin Endocrinol Metab. 2005 May;90(5):2851-4
references: 15713712
references: Neuroimage. 2000 Jun;11(6 Pt 1):805-21
references: 10860804
references: Hum Reprod Update. 2010 May-Jun;16(3):276-92
references: 19926661
references: Hum Brain Mapp. 2010 Mar;31(3):353-64
references: 19662657
references: Endocrinology. 1999 Jun;140(6):2755-62
references: 10342866
references: Neuroendocrinology. 2000 Mar;71(3):187-95
references: 10729790
references: Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4569-74
references: 10200303
references: Neuroimage. 2002 Sep;17(1):29-46
references: 12482066
references: J Neurosci. 2001 Aug 15;21(16):6283-91
references: 11487651
references: Prog Neuropsychopharmacol Biol Psychiatry. 2002 Dec;26(7-8):1285-9
references: 12502015
references: J Biol Chem. 2008 Jun 27;283(26):18238-47
references: 18367451
references: Horm Metab Res. 2009 Feb;41(2):164-7
references: 18726825
references: J Clin Invest. 2008 Jul;118(7):2583-91
references: 18568078
references: Ann Neurol. 2008 May;63(5):652-7
references: 18409192
references: Neuro Endocrinol Lett. 2006 Feb-Apr;27(1-2):177-82
references: 16670672
references: Biochim Biophys Acta. 2009 May;1792(5):401-8
references: 19130879
references: J Clin Endocrinol Metab. 2010 Feb;95(2):851-5
references: 20061423
references: Am J Physiol Endocrinol Metab. 2008 Dec;295(6):E1401-8
references: 18854428
references: Arq Bras Endocrinol Metabol. 2010 Nov;54(8):690-7
references: 21340154
references: Science. 2007 Sep 7;317(5843):1355
references: 17690262
references: Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4531-6
references: 15070752
references: Science. 1995 Jul 28;269(5223):540-3
references: 7624776
references: Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):12040-5
references: 8876259
references: J Clin Endocrinol Metab. 1999 Oct;84(10):3686-95
references: 10523015
references: Neurosci Lett. 2008 Jun 13;438(1):17-21
references: 18472337
references: Neuroimage. 2006 Jul 15;31(4):1419-25
references: 16545583