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Transplantation of adipose tissue lacking PAI-1 improves glucose tolerance and attenuates cardiac metabolic abnormalities in high-fat diet-induced obesity.
Adipocyte ( IF 3.5 ) Pub Date : 2020-04-11 , DOI: 10.1080/21623945.2020.1748961
Sijing Liu 1, 2 , Yi Li 1, 2 , Xin Fan 1, 2 , Kai Li 1, 2 , Chunrong Xu 1, 2 , Liping Zhang 1, 2 , Mao Luo 1, 2 , Liqun Wang 1, 2 , Rong Li 1, 2 , Jianbo Wu 1, 2
Affiliation  

Adipose tissue is an important metabolic organ, and transplantation of white adipose tissue plays crucial roles in glucose homoeostasis and energy metabolism. However, how adipose tissue affects glucose utilization is poorly understood. PAI-1-knockout (PAI-1KO) mice were previously shown to be resistant to a high-fat diet and obesity. We used microPET/CT (positron emission tomography/computed tomography), gene microarray, and biochemical assays to measure changes in systemic and myocardial glucose metabolism in mice subjected to transplantation of adipose tissue from PAI-1KO and wild-type mice. Here, we show that transplanting subcutaneous white adipose tissue (scWAT) from PAI-1KO mice into high-fat diet (HFD)-fed mice reduced levels of serum total cholesterol and triglycerides, and improved glucose tolerance in the HFD-fed mice. microPET/CT imaging revealed that cardiac glucose uptake was increased in the heart but not in the liver, hindlimb muscles, or abdominal subcutaneous white adipose tissue in HFD-fed mice transplanted with PAI-1KO scWAT, suggesting that the transplanted PAI-1KO scWAT exerted endocrine effects in the heart. In addition, transplantation of scWAT from PAI-1KO mice upregulated mitochondrial gene expression in cardiac muscle, increased the expression of glucose transporters 1 and 4 in cardiac tissues and was associated with an increased NAD+/NADH ratio. Together, these findings suggest that modulating PAI-1 in scWAT may provide a promising approach for intervening in glucose metabolism.

中文翻译:

缺乏PAI-1的脂肪组织的移植改善了高脂饮食诱导的肥胖症患者的葡萄糖耐量并减轻了心脏代谢异常。

脂肪组织是重要的代谢器官,白色脂肪组织的移植在葡萄糖稳态和能量代谢中起着至关重要的作用。但是,人们对脂肪组织如何影响葡萄糖利用的了解很少。PAI-1基因敲除(PAI-1KO)小鼠先前被证明对高脂饮食和肥胖症有抵抗力。我们使用microPET / CT(正电子发射断层扫描/计算机断层扫描),基因芯片和生化分析来测量从PAI-1KO和野生型小鼠移植脂肪组织的小鼠体内全身和心肌葡萄糖代谢的变化。在这里,我们显示了将PAI-1KO小鼠的皮下白色脂肪组织(scWAT)移植到高脂饮食(HFD)喂养的小鼠体内可降低血清总胆固醇和甘油三酸酯的水平,并改善了HFD喂养的小鼠对葡萄糖的耐受性。microPET / CT成像显示,在用PAI-1KO scWAT移植的HFD喂养的小鼠中,心脏中的心脏葡萄糖摄取增加,但肝脏,后肢肌肉或腹部皮下白色脂肪组织中的摄取却没有增加,这表明移植的PAI-1KO scWAT发挥了作用心脏的内分泌作用。此外,从PAI-1KO小鼠移植scWAT可以上调心肌中线粒体基因的表达,增加心肌组织中葡萄糖转运蛋白1和4的表达,并与增加NAD + / NADH的比例有关。在一起,这些发现表明,调节scWAT中的PAI-1可能为干预葡萄糖代谢提供一种有前途的方法。移植有PAI-1KO scWAT的HFD喂养的小鼠的腹部或腹部皮下白色脂肪组织,这表明移植的PAI-1KO scWAT在心脏中发挥了内分泌作用。此外,从PAI-1KO小鼠移植scWAT可以上调心肌中线粒体基因的表达,增加心肌组织中葡萄糖转运蛋白1和4的表达,并与增加NAD + / NADH的比例有关。在一起,这些发现表明,调节scWAT中的PAI-1可能为干预葡萄糖代谢提供一种有前途的方法。移植有PAI-1KO scWAT的HFD喂养的小鼠的腹部或腹部皮下白色脂肪组织,这表明移植的PAI-1KO scWAT在心脏中发挥了内分泌作用。此外,从PAI-1KO小鼠移植scWAT可以上调心肌中线粒体基因的表达,增加心肌组织中葡萄糖转运蛋白1和4的表达,并与增加NAD + / NADH的比例有关。在一起,这些发现表明,调节scWAT中的PAI-1可能为干预葡萄糖代谢提供一种有前途的方法。增加了心脏组织中葡萄糖转运蛋白1和4的表达,并与NAD + / NADH比率增加有关。在一起,这些发现表明,调节scWAT中的PAI-1可能为干预葡萄糖代谢提供一种有前途的方法。增加了心脏组织中葡萄糖转运蛋白1和4的表达,并与NAD + / NADH比增加有关。在一起,这些发现表明,调节scWAT中的PAI-1可能为干预葡萄糖代谢提供一种有前途的方法。
更新日期:2020-04-20
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