PMID- 26159107
OWN - NLM
STAT- MEDLINE
DCOM- 20160523
LR  - 20190212
IS  - 1421-9778 (Electronic)
IS  - 1015-8987 (Linking)
VI  - 36
IP  - 4
DP  - 2015
TI  - Effect of TNF-Alpha on Caveolin-1 Expression and Insulin Signaling During 
      Adipocyte Differentiation and in Mature Adipocytes.
PG  - 1499-516
AB  - BACKGROUND/AIMS: Tumor necrosis factor-alpha (TNF-alpha)-mediated chronic low-grade 
      inflammation of adipose tissue is associated with obesity and insulin resistance. 
      Caveolin-1 (Cav-1) is the central component of adipocyte caveolae and has an 
      essential role in the regulation of insulin signaling. The effects of TNF-alpha on 
      Cav-1 expression and insulin signaling during adipocyte differentiation and in 
      mature adipocytes were studied. METHODS: 3T3-L1 cells were differentiated (21 
      days) in the presence TNF-alpha (10 ng/mL) and mature adipocytes were also treated 
      with TNF-alpha for 48 hours. Cav-1 and insulin receptor (IR) gene methylation were 
      determined as well as Cav-1, IR, PKB/AKT-2 and Glut-4 expression and activation 
      by real time RT-PCR and western blot. Baseline and insulin-induced glucose uptake 
      was measured by the 2-[C14]-deoxyglucose uptake assay. RESULTS: TNF-alpha slowed down 
      the differentiation program, hindering the expression of some insulin signaling 
      intermediates without fully eliminating insulin-mediated glucose uptake. In 
      mature adipocytes, TNF-alpha did not compromise lipid-storage capacity, but 
      downregulated the expression of the insulin signaling intermediates, totally 
      blocking insulin-mediated glucose uptake. Insulin sensitivity correlated with the 
      level of activated phospho-Cav-1 in both situations, strongly suggesting the 
      direct contribution of Cav-1 to the maintenance of this physiological response. 
      CONCLUSION: Cav-1 activation by phosphorylation seems to be essential for the 
      maintenance of an active and insulin-sensitive glucose uptake.
CI  - (c) 2015 S. Karger AG, Basel.
FAU - Palacios-Ortega, Sara
AU  - Palacios-Ortega S
FAU - Varela-Guruceaga, Maider
AU  - Varela-Guruceaga M
FAU - Algarabel, Miriam
AU  - Algarabel M
FAU - Ignacio Milagro, Fermin
AU  - Ignacio Milagro F
FAU - Alfredo Martinez, J
AU  - Alfredo Martinez J
FAU - de Miguel, Carlos
AU  - de Miguel C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Cell Physiol Biochem
JT  - Cellular physiology and biochemistry : international journal of experimental 
      cellular physiology, biochemistry, and pharmacology
JID - 9113221
RN  - 0 (Adipokines)
RN  - 0 (Caveolin 1)
RN  - 0 (Insulin)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adipocytes/*cytology/metabolism
MH  - *Adipogenesis
MH  - Adipokines/metabolism
MH  - Animals
MH  - Caveolin 1/*genetics/metabolism
MH  - Cell Survival
MH  - DNA Methylation
MH  - Gene Expression Regulation
MH  - Glucose/metabolism
MH  - Insulin/*metabolism
MH  - Insulin Resistance
MH  - Lipid Metabolism
MH  - Mice
MH  - Phosphorylation
MH  - Signal Transduction
MH  - Tumor Necrosis Factor-alpha/*metabolism
EDAT- 2015/07/15 06:00
MHDA- 2016/05/24 06:00
CRDT- 2015/07/11 06:00
PHST- 2015/04/22 00:00 [accepted]
PHST- 2015/07/11 06:00 [entrez]
PHST- 2015/07/15 06:00 [pubmed]
PHST- 2016/05/24 06:00 [medline]
AID - 000430314 [pii]
AID - 10.1159/000430314 [doi]
PST - ppublish
SO  - Cell Physiol Biochem. 2015;36(4):1499-516. doi: 10.1159/000430314.