骨钙素通过抑制脂肪组织炎症改善肥胖小鼠胰岛素敏感性

摘要

AIM:To explore the improving effect of osteocalcin on obesity-related insulin resistance and in-flammation in the adipose tissue of obese mice .METHODS:The C57BL/6 mice were fed with high-fat diet for 12 weeks to obtain obese mice.Osteocalcin (30 ng/kg or 3 ng/kg) and saline solution (control) were intraperitoneally injected for other 4 weeks.The fat mass, body weight, serum triglycerides and serum free fatty acid were analyzed .Intraperitoneal glu-cose tolerance test and insulin tolerance test were carried out .Macrophage infiltration degree in the adipose tissue was ob-served by immunohistochemical staining .The mRNA expression of monocyte chemotactic protein-1 ( MCP-1 ) and CD68 was detected by real-time fluorescence quantitative PCR .RESULTS:Osteocalcin (30 ng/kg or 3 ng/kg) treatment for 4 weeks significantly reduced the body weight , fat mass and insulin level , and improved abnormal glucose tolerance and insu-lin resistance in the obese mice .Moreover, the macrophage infiltration decreased , and the mRNA expression of MCP-1 and CD68 was down-regulated in the adipose tissue of obese mice treated with osteocalcin at 30 ng/kg.CONCLUSION:Os-teocalcin at 30 ng/kg significantly reduces body weight and fat mass , and attenuates the severity of insulin resistance through down-regulating the mRNA expression of MCP-1 and CD68 and inbihiting macrophage infiltration in the adipose tis-sue of obese mice induced by high-fat diet.%目的：为探讨骨钙素改善肥胖相关胰岛素抵抗的机制，我们观察了骨钙素对饮食诱导的肥胖小鼠脂肪组织中炎症的影响。方法：C57BL／6小鼠以高脂饮食喂养12周后，对肥胖小鼠每日腹腔注射骨钙素（30 ng／kg或3 ng／kg），对照组以等体积的生理盐水处理。测定各组小鼠体重、体脂、血清甘油三酯和血清游离脂肪酸的变化；进行葡萄糖耐量试验和胰岛素耐量试验；免疫组化染色观察巨噬细胞向脂肪组织的浸润程度及巨噬细胞标志物CD68的蛋白表达量；实时荧光定量PCR检测单核细胞趋化蛋白1（ MCP-1）及CD68的mRNA表达。结果：骨钙素（30 ng／kg或者3 ng／kg）处理4周，能降低HFD小鼠的体重、体脂量、空腹胰岛素水平，改善其糖耐量异常和胰岛素抵抗。此外，在骨钙素（30 ng／kg）治疗肥胖小鼠脂肪组织巨噬细胞的浸润减少，脂肪组织中MCP-1与CD68 mR-NA表达明显降低。结论：骨钙素（30 ng／kg）通过下调CD68和MCP-1表达，抑制肥胖小鼠脂肪组织巨噬细胞聚集及MCP-1分泌，降低小鼠体重和体内脂肪含量，改善了肥胖小鼠的胰岛素敏感性。