PMID- 23011922
OWN - NLM
STAT- MEDLINE
DCOM- 20130117
LR  - 20211021
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 153
IP  - 11
DP  - 2012 Nov
TI  - Central depletion of brain-derived neurotrophic factor in mice results in high 
      bone mass and metabolic phenotype.
PG  - 5394-405
LID - 10.1210/en.2012-1378 [doi]
AB  - Brain-derived neurotrophic factor (BDNF) plays important roles in neuronal 
      differentiation/survival, the regulation of food intake, and the pathobiology of 
      obesity and type 2 diabetes mellitus. BDNF and its receptor are expressed in 
      osteoblasts and chondrocyte. BDNF in vitro has a positive effect on bone; whether 
      central BDNF affects bone mass in vivo is not known. We therefore examined bone 
      mass and energy use in brain-targeted BDNF conditional knockout mice 
      (Bdnf(2lox/2lox)/93). The deletion of BDNF in the brain led to a metabolic 
      phenotype characterized by hyperphagia, obesity, and increased abdominal white 
      adipose tissue. Central BDNF deletion produces a marked skeletal phenotype 
      characterized by increased femur length, elevated whole bone mineral density, and 
      bone mineral content. The skeletal changes are developmentally regulated and 
      appear concurrently with the metabolic phenotype, suggesting that the metabolic 
      and skeletal actions of BDNF are linked. The increased bone development is 
      evident in both the cortical and trabecular regions. Compared with control, 
      Bdnf(2lox/2lox)/93 mice show greater trabecular bone volume (+50% for distal 
      femur, P < 0.001; +35% for vertebral body, P < 0.001) and midfemoral cortical 
      thickness (+11 to 17%, P < 0.05), measured at 3 and 6 months of age. The skeletal 
      and metabolic phenotypes were gender dependent, with female being more affected 
      than male mice. However, uncoupling protein-1 expression in brown fat, a marker 
      of sympathetic tone, was not different between genotypes. We show that deletion 
      of central BDNF expression in mice results in increased bone mass and white 
      adipose tissue, with no significant changes in sympathetic signaling or 
      peripheral serotonin, associated with hyperphagia, obesity, and leptin 
      resistance.
FAU - Camerino, C
AU  - Camerino C
AD  - Harvard School of Dental Medicine, Boston, Massachusetts 02115, USA. 
      ccamerino@libero.it
FAU - Zayzafoon, M
AU  - Zayzafoon M
FAU - Rymaszewski, M
AU  - Rymaszewski M
FAU - Heiny, J
AU  - Heiny J
FAU - Rios, M
AU  - Rios M
FAU - Hauschka, P V
AU  - Hauschka PV
LA  - eng
GR  - P30 AR046031/AR/NIAMS NIH HHS/United States
GR  - R01 DK073311/DK/NIDDK NIH HHS/United States
GR  - P30-AR46031/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120925
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Ion Channels)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Ucp1 protein, mouse)
RN  - 0 (Uncoupling Protein 1)
RN  - 333DO1RDJY (Serotonin)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Adipose Tissue, White/*metabolism
MH  - Animals
MH  - Bone Density/*genetics
MH  - Bone and Bones/*metabolism
MH  - Brain/metabolism
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Eating/genetics
MH  - Female
MH  - Hyperphagia/genetics/*metabolism
MH  - Ion Channels/genetics/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Mitochondrial Proteins/genetics/metabolism
MH  - Norepinephrine/metabolism
MH  - Obesity/genetics/*metabolism
MH  - Serotonin/metabolism
MH  - Sex Factors
MH  - Uncoupling Protein 1
PMC - PMC3685798
EDAT- 2012/09/27 06:00
MHDA- 2013/01/18 06:00
PMCR- 2013/11/01
CRDT- 2012/09/27 06:00
PHST- 2012/09/27 06:00 [entrez]
PHST- 2012/09/27 06:00 [pubmed]
PHST- 2013/01/18 06:00 [medline]
PHST- 2013/11/01 00:00 [pmc-release]
AID - en.2012-1378 [pii]
AID - EN-12-1378 [pii]
AID - 10.1210/en.2012-1378 [doi]
PST - ppublish
SO  - Endocrinology. 2012 Nov;153(11):5394-405. doi: 10.1210/en.2012-1378. Epub 2012 
      Sep 25.