PMID- 23907013
OWN - NLM
STAT- MEDLINE
DCOM- 20140108
LR  - 20151119
IS  - 1879-1220 (Electronic)
IS  - 0960-0760 (Linking)
VI  - 138
DP  - 2013 Nov
TI  - Effects of orexin A on GLUT4 expression and lipid content via MAPK signaling in 
      3T3-L1 adipocytes.
PG  - 376-83
LID - S0960-0760(13)00134-9 [pii]
LID - 10.1016/j.jsbmb.2013.07.005 [doi]
AB  - Orexin A regulates food intake, energy metabolism and gastrointestinal function; 
      it also increases glucose uptake and inhibits lipolysis, suggesting a role for 
      orexin A in glucose and lipid metabolism. In this study, the effects of orexin A 
      on glucose transporter 4 (GLUT4) mRNA level and lipid content were explored in 
      3T3-L1 preadipocytes and adipocytes. Orexin receptor 1 (OX1R) protein expression 
      was determined in the adipose tissue of normal and obese rats. In addition, 
      3T3-L1 preadipocytes and differentiated 3T3-L1 adipocytes were incubated with 
      different concentrations of orexin A (10(-9) to 10(-7)M), without or with OX1R 
      specific antagonist, then the peroxisome proliferator-activated receptor-gamma2 
      (PPARgamma2) mRNA expression was analyzed. Differentiated 3T3-L1 adipocytes were 
      exposed to orexin A, without or with MAPK and OX1R antagonist, after which the 
      GLUT4 and ERK1/2, JNK, and p38 MAPK activation, and triglyceride (TG) content 
      were measured. We observed that OX1R protein expression was decreased in obese 
      rats, and OX1R protein level was negatively correlated with body fat, Lee's 
      index, TG, total cholesterol, and fasting insulin levels. Orexin A enhanced 
      PPARgamma2 mRNA expression in a dose-dependent manner in 3T3-L1 preadipocytes through 
      OX1R. In differentiated 3T3-L1 adipocytes, orexin A significantly increased GLUT4 
      mRNA levels, which was blocked by the ERK1/2, JNK, and p38 MAPK inhibitors as 
      well as OX1R antagonist. Furthermore, orexin A increased cellular TG content via 
      ERK1/2, JNK, and p38 MAPK as well as OX1R. Thus, orexin A increases GLUT4 mRNA 
      expression and lipid accumulation in differentiated 3T3-L1 adipocytes via ERK1/2, 
      JNK, and p38 MAPK signaling. In addition, orexin A increases PPARgamma2 mRNA 
      expression in 3T3-L1 preadipocytes. Further studies are necessary to elucidate 
      the impact of orexin A in metabolic disorders and adipocyte differentiation.
CI  - Crown Copyright (c) 2013. Published by Elsevier Ltd. All rights reserved.
FAU - Shen, Yang
AU  - Shen Y
AD  - Department of Endocrinology, First Affiliated Hospital, China Medical University, 
      Shenyang, Liaoning 110001, PR China.
FAU - Zhao, Yuyan
AU  - Zhao Y
FAU - Zheng, Delu
AU  - Zheng D
FAU - Chang, Xiaocen
AU  - Chang X
FAU - Ju, Shujing
AU  - Ju S
FAU - Guo, Lei
AU  - Guo L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130729
PL  - England
TA  - J Steroid Biochem Mol Biol
JT  - The Journal of steroid biochemistry and molecular biology
JID - 9015483
RN  - 0 (Glucose Transporter Type 4)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Neuropeptides)
RN  - 0 (Orexins)
RN  - 0 (Peroxisome Proliferator-Activated Receptors)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adipocytes/*drug effects/*metabolism
MH  - Animals
MH  - Glucose Transporter Type 4/genetics/*metabolism
MH  - Intracellular Signaling Peptides and Proteins/*pharmacology
MH  - MAP Kinase Signaling System/drug effects/genetics
MH  - Male
MH  - Mice
MH  - Mitogen-Activated Protein Kinases/genetics/*metabolism
MH  - Neuropeptides/*pharmacology
MH  - Orexins
MH  - Peroxisome Proliferator-Activated Receptors/genetics/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - p38 Mitogen-Activated Protein Kinases/genetics/metabolism
OTO - NOTNLM
OT  - Adipocytes
OT  - GLUT4
OT  - Orexin A
OT  - PPARgamma
EDAT- 2013/08/03 06:00
MHDA- 2014/01/09 06:00
CRDT- 2013/08/03 06:00
PHST- 2013/03/11 00:00 [received]
PHST- 2013/07/16 00:00 [revised]
PHST- 2013/07/22 00:00 [accepted]
PHST- 2013/08/03 06:00 [entrez]
PHST- 2013/08/03 06:00 [pubmed]
PHST- 2014/01/09 06:00 [medline]
AID - S0960-0760(13)00134-9 [pii]
AID - 10.1016/j.jsbmb.2013.07.005 [doi]
PST - ppublish
SO  - J Steroid Biochem Mol Biol. 2013 Nov;138:376-83. doi: 
      10.1016/j.jsbmb.2013.07.005. Epub 2013 Jul 29.