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.
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Authors | Chikage Sato, Kenichi Shikata, Daisho Hirota, Motofumi Sasaki, Shingo Nishishita, Satoshi Miyamoto, Ryo Kodera, Daisuke Ogawa, Atsuhito Tone, Hitomi Usui Kataoka, Jun Wada, Nobuo Kajitani, Hirofumi Makino |
Journal | Diabetes
(Diabetes)
Vol. 60
Issue 1
Pg. 189-99
(Jan 2011)
ISSN: 1939-327X [Electronic] United States |
PMID | 20971965
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- DNA Primers
- E-Selectin
- Insulin
- Membrane Glycoproteins
- P-Selectin
- P-selectin ligand protein
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Topics |
- Adipocytes
(physiology)
- Animals
- DNA Primers
- Diet, Fat-Restricted
- E-Selectin
(genetics)
- Fatty Liver
(prevention & control)
- Flow Cytometry
- Gene Expression Profiling
- Glucose Tolerance Test
- Humans
- Inflammation
(genetics, physiopathology)
- Insulin
(pharmacology)
- Insulin Resistance
(genetics, physiology)
- Membrane Glycoproteins
(deficiency, genetics)
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Obesity
(genetics, prevention & control)
- Oligonucleotide Array Sequence Analysis
- P-Selectin
(genetics)
- Phosphorylation
- Reverse Transcriptase Polymerase Chain Reaction
- Up-Regulation
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