PMID- 28721258
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 2056-3973 (Print)
IS  - 2056-3973 (Electronic)
IS  - 2056-3973 (Linking)
VI  - 1
DP  - 2015
TI  - Role of the central nervous system and adipose tissue BDNF/TrkB axes in metabolic 
      regulation.
PG  - 15009
LID - 10.1038/npjamd.2015.9 [doi]
AB  - BACKGROUND/OBJECTIVES: Brain-derived neurotrophic factor (BDNF) and its receptor 
      (tropomyosin-related kinase B: TrkB, also known as Ntrk2) have a key role in 
      central regulation of the energy balance. BDNF and TrkB are also expressed in the 
      peripheral tissues, including adipose tissue, but their peripheral role has been 
      unclear. Here we report on the functional significance of the adipose tissue 
      BDNF/TrkB axis in metabolic homeostasis. MATERIALS AND METHODS: To examine the 
      role of the BDNF/TrkB axis in the central nervous system and in adipose tissue, 
      we generated adipocyte-specific or neuron-specific BDNF/TrkB conditional knockout 
      (CKO) mice. Then we compared the feeding behavior and metabolic profile between 
      each type of CKO mouse and their littermates. RESULTS: Bdnf expression was 
      significantly increased in the adipose tissue of mice receiving a high-calorie 
      diet, whereas Ntrk2 expression was decreased. The Bdnf/Ntrk2 expression ratio of 
      adipose tissue was higher in female mice than male mice. Fabp4-Cre mice are 
      widely used to establish adipocyte-specific CKO mice. However, we found that 
      Fabp4-Cre-induced deletion of Bdnf or Ntrk2 led to hyperphagia, obesity, and 
      aggressiveness, presumably due to ectopic Fabp4-Cre mediated gene recombination 
      in the brain. Next, we attempted to more specifically delete Bdnf or Ntrk2 in 
      adipocytes using Adipoq-Cre mice. Expression of Ntrk2, but not Bdnf, in the 
      adipose tissue was reduced by Adipoq-Cre mediated gene recombination, indicating 
      that adipocytes only expressed TrkB. No phenotypic changes were detected when 
      Adipoq-Cre TrkB CKO mice were fed a normal diet, whereas female CKO mice 
      receiving a high-calorie diet showed a decrease in food intake and resistance to 
      obesity. CONCLUSIONS: The adipose tissue BDNF/TrkB axis has a substantial 
      influence on the feeding behavior and obesity in female mice.
FAU - Nakagomi, Atsushi
AU  - Nakagomi A
AD  - Department of Cardiovascular Medicine, Chiba University Graduate School of 
      Medicine, Chiba, Japan.
FAU - Okada, Sho
AU  - Okada S
AD  - Department of Cardiovascular Medicine, Chiba University Graduate School of 
      Medicine, Chiba, Japan.
FAU - Yokoyama, Masataka
AU  - Yokoyama M
AD  - Department of Cardiovascular Medicine, Chiba University Graduate School of 
      Medicine, Chiba, Japan.
FAU - Yoshida, Yohko
AU  - Yoshida Y
AD  - Department of Cardiovascular Biology and Medicine, Niigata University Graduate 
      School of Medical and Dental Sciences, Niigata, Japan.
FAU - Shimizu, Ippei
AU  - Shimizu I
AD  - Department of Cardiovascular Biology and Medicine, Niigata University Graduate 
      School of Medical and Dental Sciences, Niigata, Japan.
FAU - Miki, Takashi
AU  - Miki T
AD  - Department of Medical Physiology, Chiba University Graduate School of Medicine, 
      Chiba, Japan.
FAU - Kobayashi, Yoshio
AU  - Kobayashi Y
AD  - Department of Cardiovascular Medicine, Chiba University Graduate School of 
      Medicine, Chiba, Japan.
FAU - Minamino, Tohru
AU  - Minamino T
AD  - Department of Cardiovascular Biology and Medicine, Niigata University Graduate 
      School of Medical and Dental Sciences, Niigata, Japan.
AD  - PRESTO, Japan Science and Technology Agency, Saitama, Japan.
LA  - eng
PT  - Journal Article
DEP - 20151029
PL  - England
TA  - NPJ Aging Mech Dis
JT  - NPJ aging and mechanisms of disease
JID - 101678947
PMC - PMC5514989
COIS- The authors declare no conflict of interest.
EDAT- 2015/10/29 00:00
MHDA- 2015/10/29 00:01
PMCR- 2015/10/29
CRDT- 2017/07/20 06:00
PHST- 2014/12/10 00:00 [received]
PHST- 2015/06/11 00:00 [revised]
PHST- 2015/07/31 00:00 [accepted]
PHST- 2017/07/20 06:00 [entrez]
PHST- 2015/10/29 00:00 [pubmed]
PHST- 2015/10/29 00:01 [medline]
PHST- 2015/10/29 00:00 [pmc-release]
AID - npjamd20159 [pii]
AID - 10.1038/npjamd.2015.9 [doi]
PST - epublish
SO  - NPJ Aging Mech Dis. 2015 Oct 29;1:15009. doi: 10.1038/npjamd.2015.9. eCollection 
      2015.