PMID- 28030645
OWN - NLM
STAT- MEDLINE
DCOM- 20170718
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 11
IP  - 12
DP  - 2016
TI  - Disruption of Lipid Raft Function Increases Expression and Secretion of Monocyte 
      Chemoattractant Protein-1 in 3T3-L1 Adipocytes.
PG  - e0169005
LID - 10.1371/journal.pone.0169005 [doi]
LID - e0169005
AB  - The adipocyte is unique in its capacity to store lipids. In addition to 
      triglycerides, the adipocyte stores a significant amount of cholesterol. 
      Moreover, obese adipocytes are characterized by a redistribution of cholesterol 
      with depleted cholesterol in the plasma membrane, suggesting that cholesterol 
      perturbation may play a role in adipocyte dysfunction. We used 
      methyl-beta-cyclodextrin (MbetaCD), a molecule with high affinity for cholesterol, to 
      rapidly deplete cholesterol level in differentiated 3T3-L1 adipocytes. We tested 
      whether this perturbation altered adipocyte secretion of monocyte chemoattractant 
      protein-1 (MCP-1), a chemokine that is elevated in obesity and is linked to 
      obesity-associated chronic diseases. Depletion of cholesterol by MbetaCD increased 
      MCP-1 secretion as well as the mRNA and protein levels, suggesting perturbation 
      at biosynthesis and secretion. Pharmacological inhibition revealed that NF-kappaB, 
      but not MEK, p38 and JNK, was involved in MbetaCD-stimulated MCP-1 biosynthesis and 
      secretion in adipocytes. Finally, another cholesterol-binding drug, filipin, also 
      induced MCP-1 secretion without altering membrane cholesterol level. 
      Interestingly, both MbetaCD and filipin disturbed the integrity of lipid rafts, the 
      membrane microdomains enriched in cholesterol. Thus, the depletion of membrane 
      cholesterol in obese adipocytes may result in dysfunction of lipid rafts, leading 
      to the elevation of proinflammatory signaling and MCP-1 secretion in adipocytes.
FAU - Lu, Juu-Chin
AU  - Lu JC
AUID- ORCID: 0000-0001-8523-6992
AD  - Department of Physiology and Pharmacology, Chang Gung University, Taoyuan, 
      Taiwan.
AD  - Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, 
      Taiwan.
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang 
      Gung Memorial Hospital, Linkou, Taiwan.
FAU - Chiang, Yu-Ting
AU  - Chiang YT
AD  - Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, 
      Taiwan.
FAU - Lin, Yu-Chun
AU  - Lin YC
AD  - Department of Physiology and Pharmacology, Chang Gung University, Taoyuan, 
      Taiwan.
AD  - Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, 
      Taiwan.
FAU - Chang, Yu-Tzu
AU  - Chang YT
AD  - Department of Physiology and Pharmacology, Chang Gung University, Taoyuan, 
      Taiwan.
FAU - Lu, Chia-Yun
AU  - Lu CY
AD  - Department of Physiology and Pharmacology, Chang Gung University, Taoyuan, 
      Taiwan.
AD  - Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, 
      Taiwan.
FAU - Chen, Tzu-Yu
AU  - Chen TY
AD  - Department of Biomedical Sciences, College of Medicine, Chang Gung University, 
      Taoyuan, Taiwan.
FAU - Yeh, Chia-Shan
AU  - Yeh CS
AD  - Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, 
      Taiwan.
LA  - eng
PT  - Journal Article
DEP - 20161228
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (NF-kappa B)
RN  - 0 (beta-Cyclodextrins)
RN  - 0 (methyl-beta-cyclodextrin)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adipocytes/cytology/*metabolism
MH  - Animals
MH  - Cell Differentiation
MH  - Chemokine CCL2/*metabolism
MH  - Cholesterol/*metabolism
MH  - Gene Expression Regulation/drug effects
MH  - Membrane Microdomains/metabolism/*pathology
MH  - Mice
MH  - NF-kappa B/*metabolism
MH  - Signal Transduction
MH  - beta-Cyclodextrins/pharmacology
PMC - PMC5193455
COIS- The authors have declared that no competing interests exist.
EDAT- 2016/12/29 06:00
MHDA- 2017/07/19 06:00
PMCR- 2016/12/28
CRDT- 2016/12/29 06:00
PHST- 2016/04/11 00:00 [received]
PHST- 2016/12/11 00:00 [accepted]
PHST- 2016/12/29 06:00 [entrez]
PHST- 2016/12/29 06:00 [pubmed]
PHST- 2017/07/19 06:00 [medline]
PHST- 2016/12/28 00:00 [pmc-release]
AID - PONE-D-16-14565 [pii]
AID - 10.1371/journal.pone.0169005 [doi]
PST - epublish
SO  - PLoS One. 2016 Dec 28;11(12):e0169005. doi: 10.1371/journal.pone.0169005. 
      eCollection 2016.