PMID- 26113535
OWN - NLM
STAT- MEDLINE
DCOM- 20160426
LR  - 20211203
IS  - 1539-7262 (Electronic)
IS  - 0022-2275 (Print)
IS  - 0022-2275 (Linking)
VI  - 56
IP  - 8
DP  - 2015 Aug
TI  - Foxc2 enhances proliferation and inhibits apoptosis through activating Akt/mTORC1 
      signaling pathway in mouse preadipocytes.
PG  - 1471-80
LID - 10.1194/jlr.M057679 [doi]
AB  - Forkhead box C2 (Foxc2) protein is a transcription factor in regulation of 
      development, metabolism, and immunology. However, the regulatory mechanisms of 
      Foxc2 on proliferation and apoptosis of preadipocytes are unclear. In this study, 
      we found that high-fat-diet-induced obesity elevated the expression of Foxc2 and 
      cyclin E after 6 weeks. Additionally, Foxc2 suppressed preadipocyte 
      differentiation, increased cell counts and augmented G1-S transition of 
      preadipocytes, along with the elevation of cyclin E expression and the reduction 
      levels of p27 and p53. Furthermore, Foxc2 knockdown reduced early apoptotic cells 
      with accompanying reduction of mitochondrial membrane potential and increased 
      fragmentation of genomic DNA. We show that Foxc2 reduces the expression of Bax, 
      caspase-9, and caspase-3 in both serum-starved and palmitic acid-induced cell 
      apoptotic models, which confirms the anti-apoptotic role of Foxc2. Moreover, the 
      protein kinase B (Akt)/mammalian target of rapamycin (mTOR)C1 signaling pathway 
      and the ERK/mTORC1 signaling pathway were activated along with preadipocyte 
      proliferation in response to Foxc2 overexpression, whereas apoptosis marker genes 
      were downregulated during this process. Those effects were blocked by the 
      interference of Foxc2 or signal pathways specific inhibitors. These data 
      collectively reveal that Foxc2 enhances proliferation of preadipocytes and 
      inhibits apoptosis of preadipocytes by activating the Akt/mTORC1 and ERK/mTORC1 
      signaling pathways.
CI  - Copyright (c) 2015 by the American Society for Biochemistry and Molecular Biology, 
      Inc.
FAU - Gan, Lu
AU  - Gan L
AD  - College of Animal Science and Technology, Northwest A&F University, Yangling, 
      Shaanxi 712100, China.
FAU - Liu, Zhenjiang
AU  - Liu Z
AD  - College of Animal Science and Technology, Northwest A&F University, Yangling, 
      Shaanxi 712100, China.
FAU - Jin, Wei
AU  - Jin W
AD  - College of Animal Science and Technology, Northwest A&F University, Yangling, 
      Shaanxi 712100, China.
FAU - Zhou, Zhongjie
AU  - Zhou Z
AD  - College of Animal Science and Technology, Northwest A&F University, Yangling, 
      Shaanxi 712100, China.
FAU - Sun, Chao
AU  - Sun C
AD  - College of Animal Science and Technology, Northwest A&F University, Yangling, 
      Shaanxi 712100, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150625
PL  - United States
TA  - J Lipid Res
JT  - Journal of lipid research
JID - 0376606
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Palmitates)
RN  - 0 (mesenchyme fork head 1 protein)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adipocytes/cytology
MH  - Animals
MH  - *Apoptosis/drug effects
MH  - Cell Count
MH  - Cell Cycle/drug effects
MH  - *Cell Differentiation/drug effects
MH  - Fibroblasts/*cytology/drug effects
MH  - Forkhead Transcription Factors/*metabolism
MH  - Male
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Mice
MH  - Multiprotein Complexes/*metabolism
MH  - Palmitates/pharmacology
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - *Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/*metabolism
PMC - PMC4513988
OTO - NOTNLM
OT  - cell death
OT  - cell signaling
OT  - fat
OT  - forkhead box C2
OT  - protein kinase B/mammalian target of rapamycin C1 signaling pathway
OT  - transcription factor
EDAT- 2015/06/27 06:00
MHDA- 2016/04/27 06:00
PMCR- 2016/08/01
CRDT- 2015/06/27 06:00
PHST- 2015/01/13 00:00 [received]
PHST- 2015/06/27 06:00 [entrez]
PHST- 2015/06/27 06:00 [pubmed]
PHST- 2016/04/27 06:00 [medline]
PHST- 2016/08/01 00:00 [pmc-release]
AID - S0022-2275(20)35524-3 [pii]
AID - m057679 [pii]
AID - 10.1194/jlr.M057679 [doi]
PST - ppublish
SO  - J Lipid Res. 2015 Aug;56(8):1471-80. doi: 10.1194/jlr.M057679. Epub 2015 Jun 25.