PMID- 28483667
OWN - NLM
STAT- MEDLINE
DCOM- 20171201
LR  - 20180112
IS  - 1878-5875 (Electronic)
IS  - 1357-2725 (Linking)
VI  - 88
DP  - 2017 Jul
TI  - Effect of brain-derived neurotrophic factor (BDNF) on hepatocyte metabolism.
PG  - 69-74
LID - S1357-2725(17)30098-5 [pii]
LID - 10.1016/j.biocel.2017.05.008 [doi]
AB  - Brain-derived neurotrophic factor (BDNF) plays crucial roles in the development, 
      maintenance, plasticity and homeostasis of the central and peripheral nervous 
      systems. Perturbing BDNF signaling in mouse brain results in hyperphagia, 
      obesity, hyperinsulinemia and hyperglycemia. Currently, little is known whether 
      BDNF affects liver tissue directly. Our aim was to determine the metabolic 
      signaling pathways activated after BDNF treatment in hepatocytes. Unlike its 
      effect in the brain, BDNF did not lead to activation of the liver AKT pathway. 
      However, AMP protein activated kinase (AMPK) was  approximately 3 times more active and fatty 
      acid synthase (FAS)  approximately 2-fold less active, suggesting increased fatty acid 
      oxidation and reduced fatty acid synthesis. In addition, cAMP response element 
      binding protein (CREB) was  approximately 3.5-fold less active together with its output the 
      gluconeogenic transcript phosphoenolpyruvate carboxykinase (Pepck), suggesting 
      reduced gluconeogenesis. The levels of glycogen synthase kinase 3b (GSK3b) was 
       approximately 3-fold higher suggesting increased glycogen synthesis. In parallel, the 
      expression levels of the clock genes Bmal1 and Cry1, whose protein products play 
      also a metabolic role, were  approximately 2-fold increased and decreased, respectively. In 
      conclusion, BDNF binding to hepatocytes leads to activation of catabolic 
      pathways, such as fatty acid oxidation. In parallel gluconeogenesis is inhibited, 
      while glycogen storage is triggered. This metabolic state mimics that of after 
      breakfast, in which the liver continues to oxidize fat, stops gluconeogenesis and 
      replenishes glycogen stores.
CI  - Copyright (c) 2017 Elsevier Ltd. All rights reserved.
FAU - Genzer, Yoni
AU  - Genzer Y
AD  - Institute of Biochemistry, Food Science and Nutrition, Robert H. Smith Faculty of 
      Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 
      76100, Israel.
FAU - Chapnik, Nava
AU  - Chapnik N
AD  - Institute of Biochemistry, Food Science and Nutrition, Robert H. Smith Faculty of 
      Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 
      76100, Israel.
FAU - Froy, Oren
AU  - Froy O
AD  - Institute of Biochemistry, Food Science and Nutrition, Robert H. Smith Faculty of 
      Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 
      76100, Israel. Electronic address: oren.froy@mail.huji.ac.il.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170505
PL  - Netherlands
TA  - Int J Biochem Cell Biol
JT  - The international journal of biochemistry & cell biology
JID - 9508482
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 9005-79-2 (Glycogen)
RN  - EC 2.3.1.48 (CLOCK Proteins)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinases/metabolism
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - CLOCK Proteins/genetics
MH  - Gene Expression Regulation/drug effects
MH  - Gluconeogenesis/drug effects
MH  - Glycogen/metabolism
MH  - Hepatocytes/cytology/*drug effects/*metabolism
MH  - Mice
MH  - Phosphorylation/drug effects
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Signal Transduction/drug effects
OTO - NOTNLM
OT  - AMPK
OT  - BDNF
OT  - Fatty acid oxidation
OT  - Metabolism
OT  - Signaling
EDAT- 2017/05/10 06:00
MHDA- 2017/12/02 06:00
CRDT- 2017/05/10 06:00
PHST- 2017/01/21 00:00 [received]
PHST- 2017/03/28 00:00 [revised]
PHST- 2017/05/04 00:00 [accepted]
PHST- 2017/05/10 06:00 [pubmed]
PHST- 2017/12/02 06:00 [medline]
PHST- 2017/05/10 06:00 [entrez]
AID - S1357-2725(17)30098-5 [pii]
AID - 10.1016/j.biocel.2017.05.008 [doi]
PST - ppublish
SO  - Int J Biochem Cell Biol. 2017 Jul;88:69-74. doi: 10.1016/j.biocel.2017.05.008. 
      Epub 2017 May 5.