P-selectin glycoprotein ligand-1 deficiency is protective against obesity-related insulin resistance

Chikage Sato, Kenichi Shikata, Daisho Hirota, Motofumi Sasaki, Shingo Nishishita, Satoshi Miyamoto, Ryo Kodera, Daisuke Ogawa, Atsuhito Tone, Hitomi Kataoka, Jun Wada, Nobuo Kajitani, Hirofumi Makino

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)189-199
Number of pages11
JournalDiabetes
Volume60
Issue number1
DOIs
Publication statusPublished - Jan 2011

Fingerprint

Insulin Resistance
Obesity
White Adipose Tissue
High Fat Diet
Adipose Tissue
Monocytes
Obese Mice
Chemokine CCL2
Oligonucleotide Array Sequence Analysis
Macrophages
P-selectin ligand protein
Selectins
Fat-Restricted Diet
Microarray Analysis
Transcriptome
Lipid Metabolism
Chemokines
Adipocytes
Hypertrophy
Real-Time Polymerase Chain Reaction

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

P-selectin glycoprotein ligand-1 deficiency is protective against obesity-related insulin resistance. / Sato, Chikage; Shikata, Kenichi; Hirota, Daisho; Sasaki, Motofumi; Nishishita, Shingo; Miyamoto, Satoshi; Kodera, Ryo; Ogawa, Daisuke; Tone, Atsuhito; Kataoka, Hitomi; Wada, Jun; Kajitani, Nobuo; Makino, Hirofumi.

In: Diabetes, Vol. 60, No. 1, 01.2011, p. 189-199.

Research output: Contribution to journalArticle

Sato, Chikage ; Shikata, Kenichi ; Hirota, Daisho ; Sasaki, Motofumi ; Nishishita, Shingo ; Miyamoto, Satoshi ; Kodera, Ryo ; Ogawa, Daisuke ; Tone, Atsuhito ; Kataoka, Hitomi ; Wada, Jun ; Kajitani, Nobuo ; Makino, Hirofumi. / P-selectin glycoprotein ligand-1 deficiency is protective against obesity-related insulin resistance. In: Diabetes. 2011 ; Vol. 60, No. 1. pp. 189-199.
@article{5871d2257a524cf9b27adbef8dc05f71,
title = "P-selectin glycoprotein ligand-1 deficiency is protective against obesity-related insulin resistance",
abstract = "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.",
author = "Chikage Sato and Kenichi Shikata and Daisho Hirota and Motofumi Sasaki and Shingo Nishishita and Satoshi Miyamoto and Ryo Kodera and Daisuke Ogawa and Atsuhito Tone and Hitomi Kataoka and Jun Wada and Nobuo Kajitani and Hirofumi Makino",
year = "2011",
month = "1",
doi = "10.2337/db09-1894",
language = "English",
volume = "60",
pages = "189--199",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "1",

}

TY - JOUR

T1 - P-selectin glycoprotein ligand-1 deficiency is protective against obesity-related insulin resistance

AU - Sato, Chikage

AU - Shikata, Kenichi

AU - Hirota, Daisho

AU - Sasaki, Motofumi

AU - Nishishita, Shingo

AU - Miyamoto, Satoshi

AU - Kodera, Ryo

AU - Ogawa, Daisuke

AU - Tone, Atsuhito

AU - Kataoka, Hitomi

AU - Wada, Jun

AU - Kajitani, Nobuo

AU - Makino, Hirofumi

PY - 2011/1

Y1 - 2011/1

N2 - 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.

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.

UR - http://www.scopus.com/inward/record.url?scp=78751500186&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78751500186&partnerID=8YFLogxK

U2 - 10.2337/db09-1894

DO - 10.2337/db09-1894

M3 - Article

C2 - 20971965

AN - SCOPUS:78751500186

VL - 60

SP - 189

EP - 199

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 1

ER -