Knockout of the l-pgds gene aggravates obesity and atherosclerosis in mice
Knockout of the l-pgds gene aggravates obesity and atherosclerosis in mice
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DOI：
10.1016/j.bbrc.2008.11.152
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发表时间：
2009-01-23
影响因子：
3.1
通讯作者：
Sasaguri, Toshiyuki
中科院分区：
文献类型：
--
作者：
Tanaka, Reiko;Miwa, Yoshikazu;Sasaguri, Toshiyuki
本研究旨在通过基因敲除（KO）小鼠来确定脂钙素型前列腺素D合成酶（l-pgds）缺乏是否与动脉粥样硬化有关。8周龄C57BL/6（野生型；WT）给予高脂肪饮食。l-pgds KO （LKO）、载脂蛋白E (apo E) KO （AKO）和l-pgds/apo E双KO （DKO）小鼠。l-pgds缺陷小鼠的体重显著增加，并伴有皮下和内脏脂肪组织的增大。与WT小鼠相比，高脂饮食诱导的LKO小鼠主动脉壁脂肪沉积明显增加，而AKO与DKO小鼠之间无显著差异。在LKO小鼠中，主动脉根部的动脉粥样硬化斑块也增加，巨噬细胞细胞数量和促炎细胞因子如白细胞介素-1 β和单核细胞化学吸引蛋白-1的表达显著增加。综上所述，l-pgds缺乏可能通过调节炎症反应导致肥胖并促进动脉粥样硬化。(C) 2008爱思唯尔公司版权所有。
This study was designed to determine whether lipocalin type-prostaglandin D synthase (l-pgds) deficiency contributes to atherogenesis using gene knockout (KO) mice. A high-fat diet was given to 8-week-old C57BL/6 (wild type; WT). l-pgds KO (LKO), apolipoprotein E (apo E) KO (AKO) and l-pgds/apo E double KO (DKO) mice. The l-pgds deficient mice showed significantly increased body weight, which was accompanied by increased size of subcutaneous and visceral fat tissues. Fat deposition in the aortic: wall induced by the high-fat diet was significantly increased in LKO mice compared with WT mice, although there was no significant difference between AKO and DKO mice. In LKO mice, atherosclerotic plaque in the aortic root was also increased and, furthermore, macrophage cellularity and the expression of pro-inflammatory cytokines such as interleukin-1 beta and monocyte chemoattractant protein-1 were significant increased. In conclusion, l-pgds deficiency induces obesity and facilitates atherosclerosis, probably through the regulation of inflammatory responses. (C) 2008 Elsevier Inc. All rights reserved.