PMID- 20971965
OWN - NLM
STAT- MEDLINE
DCOM- 20110225
LR  - 20211020
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 60
IP  - 1
DP  - 2011 Jan
TI  - P-selectin glycoprotein ligand-1 deficiency is protective against obesity-related 
      insulin resistance.
PG  - 189-99
LID - 10.2337/db09-1894 [doi]
AB  - OBJECTIVE: An inflammatory process is involved in the mechanism of 
      obesity-related insulin resistance. Recent studies indicate that monocyte 
      chemoattractant protein-1 (MCP-1) is a major chemokine that promotes monocyte 
      infiltration into adipose tissues; however, the adhesion pathway in adipose 
      tissues remains unclear. We aimed to clarify the adhesion molecules that mediate 
      monocyte infiltration into adipose tissue. RESEARCH DESIGN AND METHODS: We used a 
      DNA microarray to compare the gene expression profiles in epididymal white 
      adipose tissues (eWAT) between db/db mice and C57/BL6 mice each fed a high-fat 
      diet (HFD) or a low-fat diet (LFD). We investigated the change of insulin 
      resistance and inflammation in eWAT in P-selectin glycoprotein ligand-1 (PSGL-1) 
      homozygous knockout (PSGL-1(-)(/)(-)) mice compared with wild-type (WT) mice fed HFD. 
      RESULTS: DNA microarray analysis revealed that PSGL-1, a major ligand for 
      selectins, is upregulated in eWAT from both db/db mice and WT mice fed HFD. 
      Quantitative real-time RT-PCR and immunohistochemistry showed that PSGL-1 is 
      expressed on both endothelial cells and macrophages in eWAT of obese mice. 
      PSGL-1(-)(/)(-) mice fed HFD showed a remarkable reduction of macrophage accumulation 
      and expression of proinflammatory genes, including MCP-1 in eWAT. Moreover, 
      adipocyte hypertrophy, insulin resistance, lipid metabolism, and hepatic fatty 
      change were improved in PSGL-1(-)(/) (-)mice compared with WT mice fed HFD. 
      CONCLUSIONS: These results indicate that PSGL-1 is a crucial adhesion molecule 
      for the recruitment of monocytes into adipose tissues in obese mice, making it a 
      candidate for a novel therapeutic target for the prevention of obesity-related 
      insulin resistance.
FAU - Sato, Chikage
AU  - Sato C
AD  - Department of Medicine and Clinical Science, Okayama University Graduate School 
      of Medicine, Japan.
FAU - Shikata, Kenichi
AU  - Shikata K
FAU - Hirota, Daisho
AU  - Hirota D
FAU - Sasaki, Motofumi
AU  - Sasaki M
FAU - Nishishita, Shingo
AU  - Nishishita S
FAU - Miyamoto, Satoshi
AU  - Miyamoto S
FAU - Kodera, Ryo
AU  - Kodera R
FAU - Ogawa, Daisuke
AU  - Ogawa D
FAU - Tone, Atsuhito
AU  - Tone A
FAU - Kataoka, Hitomi Usui
AU  - Kataoka HU
FAU - Wada, Jun
AU  - Wada J
FAU - Kajitani, Nobuo
AU  - Kajitani N
FAU - Makino, Hirofumi
AU  - Makino H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101022
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (DNA Primers)
RN  - 0 (E-Selectin)
RN  - 0 (Insulin)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (P-Selectin)
RN  - 0 (P-selectin ligand protein)
SB  - IM
MH  - Adipocytes/physiology
MH  - Animals
MH  - DNA Primers
MH  - Diet, Fat-Restricted
MH  - E-Selectin/genetics
MH  - Fatty Liver/prevention & control
MH  - Flow Cytometry
MH  - Gene Expression Profiling
MH  - Glucose Tolerance Test
MH  - Humans
MH  - Inflammation/genetics/physiopathology
MH  - Insulin/pharmacology
MH  - Insulin Resistance/genetics/*physiology
MH  - Membrane Glycoproteins/*deficiency/genetics
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Obesity/genetics/*prevention & control
MH  - Oligonucleotide Array Sequence Analysis
MH  - P-Selectin/genetics
MH  - Phosphorylation
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Up-Regulation
PMC - PMC3012171
EDAT- 2010/10/26 06:00
MHDA- 2011/02/26 06:00
PMCR- 2012/01/01
CRDT- 2010/10/26 06:00
PHST- 2010/10/26 06:00 [entrez]
PHST- 2010/10/26 06:00 [pubmed]
PHST- 2011/02/26 06:00 [medline]
PHST- 2012/01/01 00:00 [pmc-release]
AID - db09-1894 [pii]
AID - 1894 [pii]
AID - 10.2337/db09-1894 [doi]
PST - ppublish
SO  - Diabetes. 2011 Jan;60(1):189-99. doi: 10.2337/db09-1894. Epub 2010 Oct 22.