PMID- 26549689
OWN - NLM
STAT- MEDLINE
DCOM- 20160930
LR  - 20211203
IS  - 1872-8057 (Electronic)
IS  - 0303-7207 (Linking)
VI  - 420
DP  - 2016 Jan 15
TI  - Effects of orexin A on glucose metabolism in human hepatocellular carcinoma 
      in vitro via PI3K/Akt/mTOR-dependent and -independent mechanism.
PG  - 208-16
LID - S0303-7207(15)30128-3 [pii]
LID - 10.1016/j.mce.2015.11.002 [doi]
AB  - Orexins are hypothalamic neuropeptides that regulate food intake, energy 
      homeostasis, reward system and sleep/wakefulness states. The purpose of this 
      study was to investigate the effects of orexin A on glucose metabolism in human 
      hepatocellular carcinoma cell line, Hep3B, and determine the possible mechanisms. 
      Hep3B cells were incubated with different concentrations of orexin A 
      (10(-9)-10(-7) M) in vitro in the presence or absence of the orexin receptor 1 
      (OX1R) inhibitor (SB334867), Akt inhibitor (PF-04691502) and mammalian target of 
      rapamycin (mTOR) inhibitor (temsirolimus). Subsequently, OX1R protein expression, 
      glucose transporter 1 (GLUT1) expression, glucose uptake, the mRNA expression of 
      lactate dehydrogenase (LDHA), pyruvate dehydrogenase kinase 1 (PDK1) and pyruvate 
      dehydrogenase B (PDHB), lactate generation and mitochondrial pyruvate 
      dehydrogenase (PDH) enzyme activity were measured. The activity of 
      phosphoinositide 3-kinase (PI3K)/Akt/mTOR signaling was also determined. OX1R was 
      expressed in hepatoma tissues and Hep3B cells. Stimulation of the Hep3B cells 
      with orexin A resulted in a dose-dependent increase of GLUT1 expression and 
      glucose uptake, which was associated with the activation of PI3K/Akt/mTOR 
      pathway. Further, orexin A increased PDHB expression and PDH enzyme activity, 
      decreased LDHA, PDK1 mRNA levels and lactate generation independent of 
      PI3K/Akt/mTOR pathway. Our results demonstrated that orexin A directed the 
      cellular metabolism towards mitochondrial glucose oxidation rather than 
      glycolysis. These findings provide functional evidence of the metabolic actions 
      of orexin A in hepatocellular carcinoma cells.
CI  - Copyright (c) 2015 Elsevier Ireland Ltd. All rights reserved.
FAU - Liu, Yuanyuan
AU  - Liu Y
AD  - Department of Endocrinology, First Affiliated Hospital, China Medical University, 
      Shenyang, Liaoning, 110001, PR China.
FAU - Zhao, Yuyan
AU  - Zhao Y
AD  - Department of Endocrinology, First Affiliated Hospital, China Medical University, 
      Shenyang, Liaoning, 110001, PR China.
FAU - Guo, Lei
AU  - Guo L
AD  - Department of Orthopedic Surgery, First Affiliated Hospital, China Medical 
      University, Shenyang, Liaoning, 110001, PR China. Electronic address: 
      g572@sina.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151106
PL  - Ireland
TA  - Mol Cell Endocrinol
JT  - Molecular and cellular endocrinology
JID - 7500844
RN  - 0 (Glucose Transporter Type 1)
RN  - 0 (Orexin Receptors)
RN  - 0 (Orexins)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Blotting, Western
MH  - Carcinoma, Hepatocellular/*metabolism
MH  - Cell Line, Tumor
MH  - Citric Acid Cycle/drug effects
MH  - Glucose/*metabolism
MH  - Glucose Transporter Type 1/metabolism
MH  - Glycolysis/drug effects
MH  - Humans
MH  - Immunohistochemistry
MH  - L-Lactate Dehydrogenase/metabolism
MH  - Liver Neoplasms/*metabolism
MH  - Metabolic Flux Analysis
MH  - Mitochondria/drug effects/metabolism
MH  - Orexin Receptors/metabolism
MH  - Orexins/*pharmacology
MH  - Oxidation-Reduction/drug effects
MH  - Oxidative Phosphorylation/drug effects
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/*metabolism
OTO - NOTNLM
OT  - Akt
OT  - Glucose metabolism
OT  - Hepatocellular carcinoma
OT  - Orexin A
OT  - Orexin receptor 1
OT  - mTOR
EDAT- 2015/11/10 06:00
MHDA- 2016/10/01 06:00
CRDT- 2015/11/10 06:00
PHST- 2015/08/26 00:00 [received]
PHST- 2015/10/31 00:00 [revised]
PHST- 2015/11/02 00:00 [accepted]
PHST- 2015/11/10 06:00 [entrez]
PHST- 2015/11/10 06:00 [pubmed]
PHST- 2016/10/01 06:00 [medline]
AID - S0303-7207(15)30128-3 [pii]
AID - 10.1016/j.mce.2015.11.002 [doi]
PST - ppublish
SO  - Mol Cell Endocrinol. 2016 Jan 15;420:208-16. doi: 10.1016/j.mce.2015.11.002. Epub 
      2015 Nov 6.