PMID- 23389992
OWN - NLM
STAT- MEDLINE
DCOM- 20140117
LR  - 20211203
IS  - 1439-4286 (Electronic)
IS  - 0018-5043 (Linking)
VI  - 45
IP  - 5
DP  - 2013 May
TI  - Identification of LRP16 as a negative regulator of insulin action and 
      adipogenesis in 3T3-L1 adipocytes.
PG  - 349-58
LID - 10.1055/s-0032-1331215 [doi]
AB  - Leukemia related protein 16 (LRP16) was first cloned from acute myeloid leukemia 
      cells in our laboratory. In the present study, we sought to investigate the role 
      of LRP16 in insulin action and sensitivity, using LRP16-depleted and 
      -overexpressing 3T3-L1 cells. LRP16 silencing resulted in a reduction of the 
      expression and secretion of tumor necrosis factor-alpha (TNF-alpha) and a concomitant 
      increase in the expression of peroxisome proliferator-activated receptor-gamma 
      (PPAR-gamma). Moreover, LRP16 depletion promoted insulin-induced glucose uptake and 
      adipocyte differentiation of 3T3-L1 cells. In contrast, LRP16 overexpression 
      increased TNF-alpha secretion, suppressed glucose uptake, and attenuated 3T3-L1 cell 
      differentiation. The phosphorylation levels of insulin receptor substrate 1 
      (IRS-1), phosphatidylinositide 3-kinase (PI3-K), and Akt were increased in 
      LRP16-deficient 3T3-L1 cells, and conversely, diminished in LRP16-overexpressing 
      3T3-L1 cells, when compared to the corresponding control cells. Additionally, 
      LRP16 overexpression raised the phosphorylation level of mammalian target of 
      rapamycin (mTOR). The pretreatment with rapamycin, a specific inhibitor of mTOR, 
      prevented the TNF-alpha elevation and PPAR-gamma reduction and restored the 
      phosphorylation of IRS-1, PI3-K, and Akt in LRP16-overexpressing cells. Our data 
      collectively indicate that LRP16 acts as a negative regulator of insulin action 
      and adipogenesis in 3T3-L1 adipocytes, which involves the activation of the mTOR 
      signaling pathway.
CI  - (c) Georg Thieme Verlag KG Stuttgart . New York.
FAU - Zang, L
AU  - Zang L
AD  - Department of Endocrinology, Chinese PLA General Hospital, Beijing, China.
FAU - Xue, B
AU  - Xue B
FAU - Lu, Z
AU  - Lu Z
FAU - Li, X
AU  - Li X
FAU - Yang, G
AU  - Yang G
FAU - Guo, Q
AU  - Guo Q
FAU - Ba, J
AU  - Ba J
FAU - Zou, X
AU  - Zou X
FAU - Dou, J
AU  - Dou J
FAU - Lu, J
AU  - Lu J
FAU - Pan, C
AU  - Pan C
FAU - Mu, Y
AU  - Mu Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130206
PL  - Germany
TA  - Horm Metab Res
JT  - Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et 
      metabolisme
JID - 0177722
RN  - 0 (Insulin)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (PPAR gamma)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.1.1.- (Carboxylic Ester Hydrolases)
RN  - EC 3.1.1.- (Macrod1 protein, mouse)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adipocytes/drug effects/*metabolism
MH  - Adipogenesis/*drug effects/genetics
MH  - Animals
MH  - Carboxylic Ester Hydrolases
MH  - Cell Differentiation/drug effects
MH  - Down-Regulation/drug effects
MH  - Gene Silencing/drug effects
MH  - Insulin/*pharmacology
MH  - Insulin Receptor Substrate Proteins/metabolism
MH  - Mice
MH  - Neoplasm Proteins/genetics/*metabolism
MH  - PPAR gamma/metabolism
MH  - Phosphorylation/drug effects
MH  - Signal Transduction/drug effects
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/metabolism
MH  - Transcription Factors/genetics/*metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 2013/02/08 06:00
MHDA- 2014/01/18 06:00
CRDT- 2013/02/08 06:00
PHST- 2013/02/08 06:00 [entrez]
PHST- 2013/02/08 06:00 [pubmed]
PHST- 2014/01/18 06:00 [medline]
AID - 10.1055/s-0032-1331215 [doi]
PST - ppublish
SO  - Horm Metab Res. 2013 May;45(5):349-58. doi: 10.1055/s-0032-1331215. Epub 2013 Feb 
      6.