PMID- 23069761
OWN - NLM
STAT- MEDLINE
DCOM- 20130606
LR  - 20211021
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Print)
IS  - 0306-4522 (Linking)
VI  - 229
DP  - 2013 Jan 15
TI  - Mechanism of hyperphagia contributing to obesity in brain-derived neurotrophic 
      factor knockout mice.
PG  - 176-99
LID - S0306-4522(12)01010-X [pii]
LID - 10.1016/j.neuroscience.2012.09.078 [doi]
AB  - Global-heterozygous and brain-specific homozygous knockouts (KOs) of 
      brain-derived neurotrophic factor (BDNF) cause late- and early-onset obesity, 
      respectively, both involving hyperphagia. Little is known about the mechanism 
      underlying this hyperphagia or whether BDNF loss from peripheral tissues could 
      contribute to overeating. Since global-homozygous BDNF-KO is perinatal lethal, a 
      BDNF-KO that spared sufficient brainstem BDNF to support normal health was 
      utilized to begin to address these issues. Meal pattern and microstructure 
      analyses suggested overeating of BDNF-KO mice was mediated by deficits in both 
      satiation and satiety that resulted in increased meal size and frequency and 
      implicated a reduction of vagal signaling from the gut to the brain. Meal-induced 
      c-Fos activation in the nucleus of the solitary tract, a more direct measure of 
      vagal afferent signaling, however, was not decreased in BDNF-KO mice, and thus 
      was not consistent with a vagal afferent role. Interestingly though, meal-induced 
      c-Fos activation was increased in the dorsal motor nucleus of the vagus nerve 
      (DMV) of BDNF-KO mice. This could imply that augmentation of vago-vagal digestive 
      reflexes occurred (e.g., accommodation), which would support increased meal size 
      and possibly increased meal number by reducing the increase in intragastric 
      pressure produced by a given amount of ingesta. Additionally, vagal sensory 
      neuron number in BDNF-KO mice was altered in a manner consistent with the 
      increased meal-induced activation of the DMV. These results suggest reduced BDNF 
      causes satiety and satiation deficits that support hyperphagia, possibly 
      involving augmentation of vago-vagal reflexes mediated by central pathways or 
      vagal afferents regulated by BDNF levels.
CI  - Copyright (c) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Fox, E A
AU  - Fox EA
AD  - Behavioral Neurogenetics Laboratory, Department of Psychological Sciences, Purdue 
      University, West Lafayette, IN 47907, USA. au_gc@psych.purdue.edu
FAU - Biddinger, J E
AU  - Biddinger JE
FAU - Jones, K R
AU  - Jones KR
FAU - McAdams, J
AU  - McAdams J
FAU - Worman, A
AU  - Worman A
LA  - eng
GR  - R01 NS046716/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20121013
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Proto-Oncogene Proteins c-fos)
SB  - IM
MH  - Animals
MH  - Body Composition/physiology
MH  - Body Weight/physiology
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Eating/physiology
MH  - Hyperphagia/*complications/genetics/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Neurons/metabolism
MH  - Obesity/*etiology/genetics/metabolism
MH  - Proto-Oncogene Proteins c-fos/metabolism
MH  - Solitary Nucleus/*metabolism
PMC - PMC3534937
MID - NIHMS414838
EDAT- 2012/10/17 06:00
MHDA- 2013/06/07 06:00
PMCR- 2014/01/15
CRDT- 2012/10/17 06:00
PHST- 2012/08/23 00:00 [received]
PHST- 2012/09/28 00:00 [revised]
PHST- 2012/09/28 00:00 [accepted]
PHST- 2012/10/17 06:00 [entrez]
PHST- 2012/10/17 06:00 [pubmed]
PHST- 2013/06/07 06:00 [medline]
PHST- 2014/01/15 00:00 [pmc-release]
AID - S0306-4522(12)01010-X [pii]
AID - 10.1016/j.neuroscience.2012.09.078 [doi]
PST - ppublish
SO  - Neuroscience. 2013 Jan 15;229:176-99. doi: 10.1016/j.neuroscience.2012.09.078. 
      Epub 2012 Oct 13.