help button home button Endocrine Society Molecular Endocrinology ENDO 08 Sessions Library
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Rios, M.
Right arrow Articles by Jaenisch, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rios, M.
Right arrow Articles by Jaenisch, R.
Molecular Endocrinology 15 (10): 1748-1757
Copyright © 2001 by The Endocrine Society

Conditional Deletion Of Brain-Derived Neurotrophic Factor in the Postnatal Brain Leads to Obesity and Hyperactivity

Maribel Rios, Guoping Fan, Csaba Fekete, Joseph Kelly, Brian Bates1, Ralf Kuehn, Ronald M. Lechan and Rudolf Jaenisch

Whitehead Institute for Biomedical Research (M.R., G.F., B.B., R.J.), Cambridge, Massachusetts 02142; Tupper Research Institute and Department of Medicine (C.F., J.K., R.M.L.), Division of Endocrinology, Diabetes, Metabolism and Molecular Medicine, New England Medical Center, Boston, Massachusetts 02111; Artemis Pharmaceuticals GmbH (R.K.), Cologne, Germany D-51063; Department of Neuroscience (R.M.L.), Tufts University School of Medicine, Boston, Massachusetts 02111; and Department of Biology (R.J.), Massachusetts Institute of Technology, Cambridge Massachusetts 02139

Address all correspondence and requests for reprints to: Dr. Rudolf Jaenisch, Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142. E-mail: jaenisch{at}wi.mit.edu

Brain-derived neurotrophic factor has been associated previously with the regulation of food intake. To help elucidate the role of this neurotrophin in weight regulation, we have generated conditional mutants in which brain-derived neurotrophic factor has been eliminated from the brain after birth through the use of the cre-loxP recombination system. Brain-derived neurotrophic factor conditional mutants were hyperactive after exposure to stressors and had higher levels of anxiety when evaluated in the light/dark exploration test. They also had mature onset obesity characterized by a dramatic 80–150% increase in body weight, increased linear growth, and elevated serum levels of leptin, insulin, glucose, and cholesterol. In addition, the mutants had an abnormal starvation response and elevated basal levels of POMC, an anorexigenic factor and the precursor for {alpha}-MSH. Our results demonstrate that brain derived neurotrophic factor has an essential maintenance function in the regulation of anxiety-related behavior and in food intake through central mediators in both the basal and fasted state.




This article has been cited by other articles:


Home page
 EndocrinologyHome page
B. Bariohay, J. Roux, C. Tardivel, J. Trouslard, A. Jean, and B. Lebrun
Brain-Derived Neurotrophic Factor/Tropomyosin-Related Kinase Receptor Type B Signaling Is a Downstream Effector of the Brainstem Melanocortin System in Food Intake Control
Endocrinology, June 1, 2009; 150(6): 2646 - 2653.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
S. Obici
Molecular Targets for Obesity Therapy in the Brain
Endocrinology, June 1, 2009; 150(6): 2512 - 2517.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
M. S. Byerly, J. Simon, E. Lebihan-Duval, M. J. Duclos, L. A. Cogburn, and T. E. Porter
Effects of BDNF, T3, and corticosterone on expression of the hypothalamic obesity gene network in vivo and in vitro
Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2009; 296(4): R1180 - R1189.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
L. Ma, G. F. Lopez, and R. F. Krimm
Epithelial-Derived Brain-Derived Neurotrophic Factor Is Required for Gustatory Neuron Targeting during a Critical Developmental Period
J. Neurosci., March 18, 2009; 29(11): 3354 - 3364.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
L. Carim-Todd, K. G. Bath, G. Fulgenzi, S. Yanpallewar, D. Jing, C. A. Barrick, J. Becker, H. Buckley, S. G. Dorsey, F. S. Lee, et al.
Endogenous Truncated TrkB.T1 Receptor Regulates Neuronal Complexity and TrkB Kinase Receptor Function In Vivo
J. Neurosci., January 21, 2009; 29(3): 678 - 685.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
J. C. Han, Q.-R. Liu, M. Jones, R. L. Levinn, C. M. Menzie, K. S. Jefferson-George, D. C. Adler-Wailes, E. L. Sanford, F. L. Lacbawan, G. R. Uhl, et al.
Brain-Derived Neurotrophic Factor and Obesity in the WAGR Syndrome
N. Engl. J. Med., August 28, 2008; 359(9): 918 - 927.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
A. P. Fernandez, J. Serrano, L. Tessarollo, F. Cuttitta, and A. Martinez
Lack of adrenomedullin in the mouse brain results in behavioral changes, anxiety, and lower survival under stress conditions
PNAS, August 26, 2008; 105(34): 12581 - 12586.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
L. Zhao, K. W. Kim, Y. Ikeda, K. K. Anderson, L. Beck, S. Chase, S. A. Tobet, and K. L. Parker
Central Nervous System-Specific Knockout of Steroidogenic Factor 1 Results in Increased Anxiety-Like Behavior
Mol. Endocrinol., June 1, 2008; 22(6): 1403 - 1415.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
Q. Gao and T. L. Horvath
Cross-talk between estrogen and leptin signaling in the hypothalamus
Am J Physiol Endocrinol Metab, May 1, 2008; 294(5): E817 - E826.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
F. F. Chehab
Minireview: Obesity and LipOdystrophy--Where Do the Circles Intersect?
Endocrinology, March 1, 2008; 149(3): 925 - 934.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
D. Tsao, H. K. Thomsen, J. Chou, J. Stratton, M. Hagen, C. Loo, C. Garcia, D. L. Sloane, A. Rosenthal, and J. C. Lin
TrkB Agonists Ameliorate Obesity and Associated Metabolic Conditions in Mice
Endocrinology, March 1, 2008; 149(3): 1038 - 1048.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
L. M. Flanagan-Cato, S. J. Fluharty, E. B. Weinreb, and D. R. LaBelle
Food Restriction Alters Neuronal Morphology in the Hypothalamic Ventromedial Nucleus of Male Rats
Endocrinology, January 1, 2008; 149(1): 93 - 99.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
T. J. Unger, G. A. Calderon, L. C. Bradley, M. Sena-Esteves, and M. Rios
Selective Deletion of Bdnf in the Ventromedial and Dorsomedial Hypothalamus of Adult Mice Results in Hyperphagic Behavior and Obesity
J. Neurosci., December 26, 2007; 27(52): 14265 - 14274.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
D. M. Kurrasch, C. C. Cheung, F. Y. Lee, P. V. Tran, K. Hata, and H. A. Ingraham
The Neonatal Ventromedial Hypothalamus Transcriptome Reveals Novel Markers with Spatially Distinct Patterning
J. Neurosci., December 12, 2007; 27(50): 13624 - 13634.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. GenomicsHome page
H. Sha, J. Xu, J. Tang, J. Ding, J. Gong, X. Ge, D. Kong, and X. Gao
Disruption of a novel regulatory locus results in decreased Bdnf expression, obesity, and type 2 diabetes in mice
Physiol Genomics, October 19, 2007; 31(2): 252 - 263.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
C. Wang, E. Bomberg, C. Billington, A. Levine, and C. M. Kotz
Brain-derived neurotrophic factor in the hypothalamic paraventricular nucleus reduces energy intake
Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2007; 293(3): R1003 - R1012.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
K. Kohara, H. Yasuda, Y. Huang, N. Adachi, K. Sohya, and T. Tsumoto
A Local Reduction in Cortical GABAergic Synapses after a Loss of Endogenous Brain-Derived Neurotrophic Factor, as Revealed by Single-Cell Gene Knock-Out Method
J. Neurosci., July 4, 2007; 27(27): 7234 - 7244.
[Abstract] [Full Text] [PDF]

Home page
 PediatricsHome page
D. Ize-Ludlow, J. A. Gray, M. A. Sperling, E. M. Berry-Kravis, J. M. Milunsky, I. S. Farooqi, C. M. Rand, and D. E. Weese-Mayer
Rapid-Onset Obesity With Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation Presenting in Childhood
Pediatrics, July 1, 2007; 120(1): e179 - e188.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
J. Gray, G. S.H. Yeo, J. J. Cox, J. Morton, A.-L. R. Adlam, J. M. Keogh, J. A. Yanovski, A. El Gharbawy, J. C. Han, Y.C. L. Tung, et al.
Hyperphagia, Severe Obesity, Impaired Cognitive Function, and Hyperactivity Associated With Functional Loss of One Copy of the Brain-Derived Neurotrophic Factor (BDNF) Gene
Diabetes, December 1, 2006; 55(12): 3366 - 3371.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
Z.-Y. Chen, D. Jing, K. G. Bath, A. Ieraci, T. Khan, C.-J. Siao, D. G. Herrera, M. Toth, C. Yang, B. S. McEwen, et al.
Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior.
Science, October 6, 2006; 314(5796): 140 - 143.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
B. M. Kublaoui, J. L. Holder Jr., K. P. Tolson, T. Gemelli, and A. R. Zinn
SIM1 Overexpression Partially Rescues Agouti Yellow and Diet-Induced Obesity by Normalizing Food Intake
Endocrinology, October 1, 2006; 147(10): 4542 - 4549.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
A. H. El-Gharbawy, D. C. Adler-Wailes, M. C. Mirch, K. R. Theim, L. Ranzenhofer, M. Tanofsky-Kraff, and J. A. Yanovski
Serum Brain-Derived Neurotrophic Factor Concentrations in Lean and Overweight Children and Adolescents
J. Clin. Endocrinol. Metab., September 1, 2006; 91(9): 3548 - 3552.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
S. C. Pandey, H. Zhang, A. Roy, and K. Misra
Central and medial amygdaloid brain-derived neurotrophic factor signaling plays a critical role in alcohol-drinking and anxiety-like behaviors.
J. Neurosci., August 9, 2006; 26(32): 8320 - 8331.
[Abstract] [Full Text] [PDF]

Home page
 Phil Trans R Soc BHome page
S. O'Rahilly and I.S. Farooqi
Genetics of obesity
Phil Trans R Soc B, July 29, 2006; 361(1471): 1095 - 1105.
[Abstract] [Full Text] [PDF]

Home page
 Neurorehabil Neural RepairHome page
S. Vaynman and F. Gomez-Pinilla
License to Run: Exercise Impacts Functional Plasticity in the Intact and Injured Central Nervous System by Using Neurotrophins
Neurorehabil Neural Repair, December 1, 2005; 19(4): 283 - 295.
[Abstract] [PDF]

Home page
 EndocrinologyHome page
B. Bariohay, B. Lebrun, E. Moyse, and A. Jean
Brain-Derived Neurotrophic Factor Plays a Role as an Anorexigenic Factor in the Dorsal Vagal Complex
Endocrinology, December 1, 2005; 146(12): 5612 - 5620.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
S. Stanley, K. Wynne, B. McGowan, and S. Bloom
Hormonal Regulation of Food Intake
Physiol Rev, October 1, 2005; 85(4): 1131 - 1158.
[Abstract] [Full Text] [PDF]

Home page
 NeuroscientistHome page
L. M. Rattiner, M. Davis, and K. J. Ressler
Brain-Derived Neurotrophic Factor in Amygdala-Dependent Learning
Neuroscientist, August 1, 2005; 11(4): 323 - 333.
[Abstract] [PDF]

Home page
 J EndocrinolHome page
K. Wynne, S. Stanley, B. McGowan, and S. Bloom
Appetite control
J. Endocrinol., February 1, 2005; 184(2): 291 - 318.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
T. Hashimoto, S. E. Bergen, Q. L. Nguyen, B. Xu, L. M. Monteggia, J. N. Pierri, Z. Sun, A. R. Sampson, and D. A. Lewis
Relationship of Brain-Derived Neurotrophic Factor and Its Receptor TrkB to Altered Inhibitory Prefrontal Circuitry in Schizophrenia
J. Neurosci., January 12, 2005; 25(2): 372 - 383.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
N. N. H. McGough, D.-Y. He, M. L. Logrip, J. Jeanblanc, K. Phamluong, K. Luong, V. Kharazia, P. H. Janak, and D. Ron
RACK1 and Brain-Derived Neurotrophic Factor: A Homeostatic Pathway That Regulates Alcohol Addiction
J. Neurosci., November 17, 2004; 24(46): 10542 - 10552.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
E. E. Zhang, E. Chapeau, K. Hagihara, and G.-S. Feng
Neuronal Shp2 tyrosine phosphatase controls energy balance and metabolism
PNAS, November 9, 2004; 101(45): 16064 - 16069.
[Abstract] [Full Text] [PDF]

Home page
 Psychosom. Med.Home page
P. Monteleone, A. Tortorella, V. Martiadis, C. Serritella, A. Fuschino, and M. Maj
Opposite Changes in the Serum Brain-Derived Neurotrophic Factor in Anorexia Nervosa and Obesity
Psychosom Med, September 1, 2004; 66(5): 744 - 748.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
L. M. Monteggia, M. Barrot, C. M. Powell, O. Berton, V. Galanis, T. Gemelli, S. Meuth, A. Nagy, R. W. Greene, and E. J. Nestler
Essential role of brain-derived neurotrophic factor in adult hippocampal function
PNAS, July 20, 2004; 101(29): 10827 - 10832.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
M. Ribases, M. Gratacos, F. Fernandez-Aranda, L. Bellodi, C. Boni, M. Anderluh, M. C. Cavallini, E. Cellini, D. Di Bella, S. Erzegovesi, et al.
Association of BDNF with anorexia, bulimia and age of onset of weight loss in six European populations
Hum. Mol. Genet., June 15, 2004; 13(12): 1205 - 1212.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
E. A. Fox and M. S. Byerly
A mechanism underlying mature-onset obesity: evidence from the hyperphagic phenotype of brain-derived neurotrophic factor mutants
Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2004; 286(6): R994 - R1004.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
A. Sahu
Minireview: A Hypothalamic Role in Energy Balance with Special Emphasis on Leptin
Endocrinology, June 1, 2004; 145(6): 2613 - 2620.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
S. C. Pandey, A. Roy, H. Zhang, and T. Xu
Partial Deletion of the cAMP Response Element-Binding Protein Gene Promotes Alcohol-Drinking Behaviors
J. Neurosci., May 26, 2004; 24(21): 5022 - 5030.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
W. Duan, Z. Guo, H. Jiang, M. Ware, and M. P. Mattson
Reversal of Behavioral and Metabolic Abnormalities, and Insulin Resistance Syndrome, by Dietary Restriction in Mice Deficient in Brain-Derived Neurotrophic Factor
Endocrinology, June 1, 2003; 144(6): 2446 - 2453.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
W. Duan, Z. Guo, H. Jiang, M. Ware, X.-J. Li, and M. P. Mattson
Dietary restriction normalizes glucose metabolism and BDNF levels, slows disease progression, and increases survival in huntingtin mutant mice
PNAS, March 4, 2003; 100(5): 2911 - 2916.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
S. Akbarian, M. Rios, R.-J. Liu, S. J. Gold, H.-F. Fong, S. Zeiler, V. Coppola, L. Tessarollo, K. R. Jones, E. J. Nestler, et al.
Brain-Derived Neurotrophic Factor Is Essential for Opiate-Induced Plasticity of Noradrenergic Neurons
J. Neurosci., May 15, 2002; 22(10): 4153 - 4162.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2001 by The Endocrine Society