Laboratory of Physiology, CNC.IBILI and Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
Instituto Politécnico de Coimbra, Coimbra Health School (ESTeSC), Department of Complementary Sciences, Coimbra, Portugal.
Sci Rep. 2017 May 10;7(1):1698. doi: 10.1038/s41598-017-01730-3.
Microvascular dysfunction has been suggested to trigger adipose tissue dysfunction in obesity. This study investigates the hypothesis that glycation impairs microvascular architecture and expandability with an impact on insulin signalling. Animal models supplemented with methylglyoxal (MG), maintained with a high-fat diet (HFD) or both (HFDMG) were studied for periepididymal adipose (pEAT) tissue hypoxia and local and systemic insulin resistance. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was used to quantify blood flow in vivo, showing MG-induced reduction of pEAT blood flow. Increased adipocyte size and leptin secretion were observed only in rats feeding the high-fat diet, without the development of hypoxia. In turn, hypoxia was only observed when MG was combined (HFDMG group), being associated with impaired activation of the insulin receptor (Tyr1163), glucose intolerance and systemic and muscle insulin resistance. Accordingly, the adipose tissue angiogenic assay has shown decreased capillarization after dose-dependent MG exposure and glyoxalase-1 inhibition. Thus, glycation impairs adipose tissue capillarization and blood flow, hampering its expandability during a high-fat diet challenge and leading to hypoxia and insulin resistance. Such events have systemic repercussions in glucose metabolism and may lead to the onset of unhealthy obesity and progression to type 2 diabetes.
微血管功能障碍被认为是肥胖导致脂肪组织功能障碍的触发因素。本研究旨在验证以下假设：糖基化会损害微血管结构和扩张能力，从而影响胰岛素信号转导。本研究通过给动物模型补充甲基乙二醛（MG）、高脂饮食（HFD）或两者结合（HFDMG），研究其附睾周围脂肪（pEAT）组织缺氧和局部及全身胰岛素抵抗情况。采用动态对比增强磁共振成像（DCE-MRI）技术来量化体内血流，结果显示 MG 诱导的 pEAT 血流减少。仅在喂食高脂肪饮食的大鼠中观察到脂肪细胞增大和瘦素分泌增加，而没有发生缺氧。相反，只有当 MG 与高脂肪饮食联合（HFDMG 组）时才会发生缺氧，同时还伴有胰岛素受体（Tyr1163）激活受损、葡萄糖耐量下降以及全身和肌肉胰岛素抵抗。相应地，脂肪组织血管生成试验显示，在受到剂量依赖性 MG 暴露和甘油醛酶-1 抑制后，毛细血管化程度降低。因此，糖基化会损害脂肪组织的毛细血管化和血流，从而在高脂肪饮食的挑战下阻碍其扩张能力，并导致缺氧和胰岛素抵抗。这些事件在葡萄糖代谢方面具有全身性影响，可能导致不健康的肥胖和 2 型糖尿病的发生。
