Adipose-derived mesenchymal stem cells improve glucose homeostasis in high-fat diet-induced obese mice.
Adipose-derived mesenchymal stem cells improve glucose homeostasis in high-fat diet-induced obese mice.
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DOI：
10.1186/s13287-015-0201-3
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发表时间：
2015-10-31
影响因子：
7.5
通讯作者：
Wang H
中科院分区：
文献类型：
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作者：
Cao M;Pan Q;Dong H;Yuan X;Li Y;Sun Z;Dong X;Wang H
目前仍缺乏治疗肥胖和糖尿病的有效方法。本研究的目的是评估单次静脉输注同基因脂肪间充质干细胞（ASC）是否可以减少肥胖，降低胰岛素抵抗，并改善高脂饮食诱导的肥胖（DIO）小鼠模型中的葡萄糖稳态。将7周龄的C57 BL/6小鼠喂食高脂肪饮食20周以产生DIO小鼠模型。以每只小鼠2 × 106个细胞的剂量对小鼠单次静脉输注离体扩增的同基因ASC。注射盐水的DIO或CHOW小鼠用作对照。在细胞输注前和输注后2周和6周获得体重、血糖水平、葡萄糖和胰岛素耐量试验结果。测定血清甘油三酯（TG）、高密度脂蛋白（HDL）和胰岛素水平。通过实时聚合酶链反应分析，在mRNA水平上测量了肝脏中与胰岛素抵抗相关的基因的表达，包括过氧化物酶体增殖物激活受体γ（PPARγ）和胰岛素受体（InsR），以及炎症（IL-6、F4/80和含有2的核苷酸结合寡聚化结构域或NOD 2）。对来自CHOW、DIO和DIO + ASC小鼠的胰腺中的β细胞质量进行定量。注射GFP+ ASC，并确定肝脏和胰腺中GFP+细胞的存在。接受ASC的DIO小鼠体重减轻，血糖水平降低，葡萄糖耐量增加。发现ASC治疗降低TG水平并增加血清HDL水平。在肝脏中，观察到脂肪细胞沉积减少，InsR和PPARγ表达增加，IL-6和F4/80表达减少。与DIO对照组相比，给药小鼠显示胰腺β细胞群保存良好，F4/80和TNF-α表达降低。在细胞注射后1周和2周，在肝脏和胰腺组织中发现GFP+细胞。ASC治疗在降低DIO小鼠的血糖水平和增加葡萄糖耐量方面是有效的。ASC的保护作用至少部分来自肝脏炎症的抑制。此外，ASC与保存较好的胰腺β细胞群相关。
Effective therapies for obesity and diabetes are still lacking. The aim of this study was to evaluate whether a single intravenous infusion of syngeneic adipose-derived mesenchymal stem cells (ASCs) can reduce obesity, lower insulin resistance, and improve glucose homeostasis in a high-fat diet-induced obese (DIO) mouse model. Seven-week-old C57BL/6 mice were fed a high-fat diet for 20 weeks to generate the DIO mouse model. Mice were given a single intravenous infusion of ex vivo expanded syngeneic ASCs at 2 × 106 cells per mouse. DIO or CHOW mice injected with saline were used as controls. Body weights, blood glucose levels, glucose, and insulin tolerance test results were obtained before and 2 and 6 weeks after cell infusion. Triglyceride (TG), high-density lipoprotein (HDL), and insulin levels in serum were measured. Expressions of genes related to insulin resistance, including peroxisome proliferator-activated receptor γ (PPARγ) and insulin receptor (InsR), and inflammation (IL-6,F4/80, and nucleotide-binding oligomerization domain containing 2, or NOD2), were measured in livers at mRNA level by real-time-polymerase chain reaction analysis. Beta-cell mass in pancrheases from CHOW, DIO, and DIO + ASC mice was quantified. GFP+ ASCs were injected, and the presence of GFP+ cells in livers and pancreases was determined. DIO mice that had received ASCs showed reduced body weights, reduced blood glucose levels, and increased glucose tolerance. ASC treatment was found to reduce TG levels and increase serum HDL levels. In livers, less fat cell deposition was observed, as were increased expression of InsR and PPARγ and reduction in expressions of IL-6 and F4/80. Treated mice showed well-preserved pancreatic β-cell mass with reduced expression of F4/80 and TNF-α compared with DIO controls. GFP+ cells were found in liver and pancreas tissues at 1 and 2 weeks after cell injection. ASC therapy is effective in lowering blood glucose levels and increasing glucose tolerance in DIO mice. The protective effects of ASCs arise at least in part from suppression of inflammation in the liver. In addition, ASCs are associated with better-preserved pancreatic β-cell mass.