Thrombospondin1 deficiency attenuates obesity-associated microvascular complications in ApoE-/- mice.
Thrombospondin1 deficiency attenuates obesity-associated microvascular complications in ApoE-/- mice.
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DOI：
10.1371/journal.pone.0121403
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Wang S
中科院分区：
文献类型：
--
作者：
Maimaitiyiming H;Clemons K;Zhou Q;Norman H;Wang S
肥胖与胰岛素抵抗和血管并发症的增加有关。以前，我们已经证明，血小板反应蛋白1（TSP 1）调节巨噬细胞的功能，并有助于肥胖相关的炎症和胰岛素抵抗。然而，TSP 1在肥胖相关血管并发症的发展中的作用尚不清楚。因此，在当前的研究中，我们研究了TSP 1缺乏是否保护ApoE-/-小鼠免于肥胖相关的微血管和大血管并发症。在这项研究中，雄性ApoE-/-小鼠和ApoE-/-TSP 1-/-小鼠喂食低脂（LF）或高脂（HF）饲料16周。我们发现，在HF喂养条件下，ApoE-/-TSP 1-/-小鼠和ApoE-/-小鼠的体重和脂肪量增加相似。然而，与肥胖的ApoE-/-小鼠相比，肥胖的ApoE-/-TSP 1-/-小鼠具有改善的葡萄糖耐量、增加的胰岛素敏感性和减少的全身炎症。这两组小鼠的主动脉粥样硬化病变形成相似。相反，与肥胖ApoE-/-小鼠相比，肥胖ApoE-/-TSP 1-/-小鼠的白蛋白尿减少，肾纤维化减少。肥胖ApoE-/-TSP 1-/-小鼠的肾功能改善与肾脂质蓄积减少相关。总之，这些数据表明，TSP 1缺乏不影响肥胖相关的大血管并发症的发展，但减弱肥胖相关的微血管并发症。
Obesity is associated with insulin resistance and the increased development of vascular complications. Previously, we have demonstrated that thrombospondin1 (TSP1) regulates macrophage function and contributes to obesity associated inflammation and insulin resistance. However, the role of TSP1 in the development of obesity associated vascular complications is not clear. Therefore, in the current study, we investigated whether TSP1 deficiency protects mice from obesity associated micro as well as macro-vascular complications in ApoE-/- mice. In this study, male ApoE-/- mice and ApoE-/-TSP1-/- mice were fed with a low-fat (LF) or a high-fat (HF) diet for 16 weeks. We found that body weight and fat mass increased similarly between the ApoE-/-TSP1-/- mice and ApoE-/- mice under HF feeding conditions. However, as compared to obese ApoE-/- mice, obese ApoE-/-TSP1-/- mice had improved glucose tolerance, increased insulin sensitivity, and reduced systemic inflammation. Aortic atherosclerotic lesion formation was similar in these two groups of mice. In contrast, albuminuria was attenuated and kidney fibrosis was reduced in obese ApoE-/-TSP1-/- mice compared to obese ApoE-/- mice. The improved kidney function in obese ApoE-/-TSP1-/- mice was associated with decreased renal lipid accumulation. Together, these data suggest that TSP1 deficiency did not affect the development of obesity associated macro-vascular complication, but attenuated obesity associated micro-vascular complications.
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影响因子：
15.9
作者：
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通讯作者：
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DOI：
10.1152/ajprenal.00209.2013
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