P-selectin glycoprotein ligand-1 deficiency is protective against obesity-related insulin resistance.
P-selectin glycoprotein ligand-1 deficiency is protective against obesity-related insulin resistance.
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作者：
Sato C;Shikata K;Hirota D;Sasaki M;Nishishita S;Miyamoto S;Kodera R;Ogawa D;Tone A;Kataoka HU;Wada J;Kajitani N;Makino H
炎症过程参与了肥胖相关胰岛素抵抗的机制。最近的研究表明，单核细胞趋化蛋白-1 （MCP-1）是促进单核细胞浸润到脂肪组织的主要趋化因子；然而，脂肪组织的粘附途径尚不清楚。我们的目的是阐明介导单核细胞浸润到脂肪组织的粘附分子。我们使用DNA微阵列比较了饲喂高脂饮食（HFD）和低脂饮食（LFD）的db/db小鼠和C57/BL6小鼠附睾白色脂肪组织（eWAT）的基因表达谱。我们研究了p -选择素糖蛋白配体-1 （PSGL-1）纯合子敲除（PSGL-1−/−）小鼠与野生型（WT）小鼠相比，胰岛素抵抗和eWAT炎症的变化。DNA微阵列分析显示，在食用HFD的db/db小鼠和WT小鼠的eWAT中，主要的选择配体PSGL-1表达上调。实时定量RT-PCR和免疫组化结果显示，PSGL-1在肥胖小鼠eWAT内皮细胞和巨噬细胞上均有表达。饲喂HFD的PSGL-1 - / -小鼠显示巨噬细胞积累和促炎基因表达显著减少，包括eWAT中MCP-1的表达。此外，与喂食HFD的WT小鼠相比，PSGL-1−/−小鼠的脂肪细胞肥大、胰岛素抵抗、脂质代谢和肝脏脂肪变化均有所改善。这些结果表明，PSGL-1是肥胖小鼠单核细胞募集到脂肪组织的关键粘附分子，使其成为预防肥胖相关胰岛素抵抗的新治疗靶点的候选物。
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. 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. 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. 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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影响因子：
7.7
作者：
Okada, S;Shikata, K;Makino, H
通讯作者：
Makino, H
影响因子：
5.5
作者：
Inoue, T;Tsuzuki, Y;Miura, S
通讯作者：
Miura, S
影响因子：
9.8
作者：
Straczkowski, M;Lewczuk, P;Kinalska, I
通讯作者：
Kinalska, I
肿瘤坏死因子-α的脂肪表达--在与肥胖相关的胰岛素抵抗中的直接作用
影响因子：
56.9
作者：
HOTAMISLIGIL, GS;SHARGILL, NS;SPIEGELMAN, BM
通讯作者：
SPIEGELMAN, BM
DOI：
10.1084/jem.20052530
发表时间：
2006-04-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Rivera-Nieves J;Burcin TL;Olson TS;Morris MA;McDuffie M;Cominelli F;Ley K
通讯作者：
Ley K