Visceral adipose tissue inflammation accelerates atherosclerosis in apolipoprotein E-deficient mice
Visceral adipose tissue inflammation accelerates atherosclerosis in apolipoprotein E-deficient mice
复制标题
DOI：
10.1161/circulationaha.107.717595
复制
发表时间：
2008-02-12
期刊：
影响因子：
37.8
通讯作者：
Eitzman, Daniel T.
中科院分区：
文献类型：
--
作者：
Ohman, Miina K.;Shen, Yuechun;Eitzman, Daniel T.
背景-脂肪炎症可能在与肥胖相关的合并症如动脉粥样硬化中起重要作用。方法和结果-为了首先建立脂肪移植的可行性，从野生型C57 BL/6 J小鼠收获附睾脂肪垫并移植到瘦素缺陷（Lep（ob/ob））小鼠中。脂肪移植产生生理瘦素水平，并防止肥胖和不育的Lep（ob/ob）小鼠。然而，移植的脂肪库与慢性增加的巨噬细胞浸润有关，其特征与从肥胖动物中收获的脂肪中观察到的特征相同。移植脂肪库中的炎症由与内源性脂肪炎症有关的相同因子调节，如单核细胞趋化蛋白-1。为了确定这种发炎的脂肪库是否会影响小鼠的血管疾病，将附睾脂肪库移植到易患动脉粥样硬化的载脂蛋白E缺陷型ApoE（-/-）小鼠中。接受脂肪移植的ApoE -/-小鼠的血浆中含有增加的瘦素、瘦素和单核细胞趋化蛋白-1，与来自假手术ApoE（-/-）小鼠的血浆相比。此外，与假手术动物相比，移植内脏脂肪的小鼠发生了显著更多的动脉粥样硬化，而皮下脂肪移植尽管有类似程度的脂肪炎症，但对动脉粥样硬化没有影响。用吡格列酮处理移植的ApoE（-/-）小鼠，降低了移植内脏脂肪垫的巨噬细胞含量，并降低了血浆单核细胞趋化蛋白-1。重要的是，吡格列酮也减少了动脉粥样硬化引发的炎症内脏脂肪，但没有保护作用动脉粥样硬化的情况下，内脏脂肪transplantation. Conclusions，我们的研究结果表明，内脏脂肪相关的炎症加速小鼠动脉粥样硬化。噻唑烷二酮类药物可能是一个有用的策略，专门减轻内脏炎症性脂肪引起的血管疾病。
Background-Fat inflammation may play an important role in comorbidities associated with obesity such as atherosclerosis.Methods and Results-To first establish feasibility of fat transplantation, epididymal fat pads were harvested from wild-type C57BL/6J mice and transplanted into leptin-deficient (Lep(ob/ob)) mice. Fat transplantation produced physiological leptin levels and prevented obesity and infertility in Lep(ob/ob) mice. However, the transplanted fat depots were associated with chronically increased macrophage infiltration with characteristics identical to those observed in fat harvested from obese animals. The inflammation in transplanted adipose depots was regulated by the same factors that have been implicated in endogenous fat inflammation such as monocyte chemoattractant protein-1. To determine whether this inflamed adipose depot could affect vascular disease in mice, epididymal fat depots were transplanted into atherosclerosis-prone apolipoprotein E-deficient ApoE(-/-) mice. Plasma from ApoE -/- mice receiving fat transplants contained increased leptin, resistin, and monocyte chemoattractant protein-1 compared with plasma from sham-operated ApoE(-/-) mice. Furthermore, mice transplanted with visceral fat developed significantly more atherosclerosis compared with sham-operated animals, whereas transplants with subcutaneous fat did not affect atherosclerosis despite a similar degree of fat inflammation. Treatment of transplanted ApoE(-/-) mice with pioglitazone decreased macrophage content of the transplanted visceral fat pad and reduced plasma monocyte chemoattractant protein-1. Importantly, pioglitazone also reduced atherosclerosis triggered by inflammatory visceral fat but had no protective effect on atherosclerosis in the absence of the visceral fat transplantation.Conclusions-Our results indicate that visceral adipose-related inflammation accelerates atherosclerosis in mice. Drugs such as thiazolidinediones might be a useful strategy to specifically attenuate the vascular disease induced by visceral inflammatory fat.