PMID- 23274913
OWN - NLM
STAT- MEDLINE
DCOM- 20140303
LR  - 20130730
IS  - 1559-0283 (Electronic)
IS  - 1085-9195 (Linking)
VI  - 66
IP  - 3
DP  - 2013 Jul
TI  - Overexpression of TFAM protects 3T3-L1 adipocytes from NYGGF4 (PID1) 
      overexpression-induced insulin resistance and mitochondrial dysfunction.
PG  - 489-97
LID - 10.1007/s12013-012-9496-1 [doi]
AB  - NYGGF4, also known as phosphotyrosine interaction domain containing 1(PID1), is a 
      recently discovered gene which is involved in obesity-related insulin resistance 
      (IR) and mitochondrial dysfunction. We aimed to further elucidate the effects and 
      mechanisms underlying NYGGF4-induced IR by investigating the effect of 
      overexpressing mitochondrial transcription factor A (TFAM), which is essential 
      for mitochondrial DNA transcription and replication, on NYGGF4-induced IR and 
      mitochondrial abnormalities in 3T3-L1 adipocytes. Overexpression of TFAM 
      increased the mitochondrial copy number and ATP content in both control 3T3-L1 
      adipocytes and NYGGF4-overexpressing adipocytes. Reactive oxygen species (ROS) 
      production was enhanced in NYGGF4-overexpressing adipocytes and reduced in 
      TFAM-overexpressing adipocytes; co-overexpression of TFAM significantly 
      attenuated ROS production in NYGGF4-overexpressing adipocytes. However, 
      overexpression of TFAM did not affect the mitochondrial transmembrane potential 
      (DeltaPsim) in control 3T3-L1 adipocytes or NYGGF4-overexpressing adipocytes. In 
      addition, co-overexpression of TFAM-enhanced insulin-stimulated glucose uptake by 
      increasing Glucose transporter type 4 (GLUT4) translocation to the PM in 
      NYGGF4-overexpressing adipocytes. Overexpression of NYGGF4 significantly 
      inhibited tyrosine phosphorylation of Insulin receptor substrate 1 (IRS-1) and 
      serine phosphorylation of Akt, whereas overexpression of TFAM strongly induced 
      phosphorylation of IRS-1 and Akt in NYGGF4-overexpressing adipocytes. This study 
      demonstrates that NYGGF4 plays a role in IR by impairing mitochondrial function, 
      and that overexpression of TFAM can restore mitochondrial function to normal 
      levels in NYGGF4-overexpressing adipocytes via activation of the IRS-1/PI3K/Akt 
      signaling pathway.
FAU - Shi, Chun-Mei
AU  - Shi CM
AD  - State Key Laboratory of Reproductive Medicine, Department of Pediatrics, Nanjing 
      Maternity and Child Health Hospital Affiliated to Nanjing Medical University, 
      Nanjing, China.
FAU - Xu, Guang-Feng
AU  - Xu GF
FAU - Yang, Lei
AU  - Yang L
FAU - Fu, Zi-Yi
AU  - Fu ZY
FAU - Chen, Ling
AU  - Chen L
FAU - Fu, Hai-Long
AU  - Fu HL
FAU - Shen, Ya-Hui
AU  - Shen YH
FAU - Zhu, Lu
AU  - Zhu L
FAU - Ji, Chen-Bo
AU  - Ji CB
FAU - Guo, Xi-Rong
AU  - Guo XR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell Biochem Biophys
JT  - Cell biochemistry and biophysics
JID - 9701934
RN  - 0 (Carrier Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Glucose Transporter Type 4)
RN  - 0 (Insulin)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (PID1 protein, human)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Transcription Factors)
RN  - 0 (mitochondrial transcription factor A)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adenosine Triphosphate/metabolism
MH  - Adipocytes/drug effects/*metabolism/*pathology
MH  - Animals
MH  - Carrier Proteins/*genetics/metabolism
MH  - DNA-Binding Proteins/*genetics/metabolism
MH  - Gene Expression
MH  - Glucose/metabolism
MH  - Glucose Transporter Type 4/metabolism
MH  - Insulin/metabolism/pharmacology
MH  - *Insulin Resistance
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Mice
MH  - Mitochondria/drug effects/metabolism/*pathology
MH  - Mitochondrial Proteins/*genetics/metabolism
MH  - Mitochondrial Size/drug effects
MH  - Phosphorylation/drug effects
MH  - Protein Transport/drug effects
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction/drug effects
MH  - Transcription Factors/*genetics/metabolism
EDAT- 2013/01/01 06:00
MHDA- 2014/03/04 06:00
CRDT- 2013/01/01 06:00
PHST- 2013/01/01 06:00 [entrez]
PHST- 2013/01/01 06:00 [pubmed]
PHST- 2014/03/04 06:00 [medline]
AID - 10.1007/s12013-012-9496-1 [doi]
PST - ppublish
SO  - Cell Biochem Biophys. 2013 Jul;66(3):489-97. doi: 10.1007/s12013-012-9496-1.