Pex11a deficiency causes dyslipidaemia and obesity in mice
Pex11a deficiency causes dyslipidaemia and obesity in mice
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DOI：
10.1111/jcmm.14108
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发表时间：
2019-03-01
影响因子：
5.3
通讯作者：
Cai, Lu
中科院分区：
文献类型：
--
作者：
Chen, Congcong;Wang, Hongwei;Cai, Lu
过氧化物酶体在脂质代谢中起核心作用。我们之前已经证明，Pex11a缺乏会损害过氧化物酶体的丰度和脂肪酸β -氧化，并导致肝脏甘油三酯积累。本文用Pex11a敲除小鼠（Pex11a(-/-)）研究了Pex11a在血脂异常和肥胖中的作用。代谢表型包括组织重量、葡萄糖耐量、胰岛素敏感性、胆固醇水平、脂肪酸谱、耗氧量和体力活动，这些代谢表型包括野生型（WT）和Pex11a（-/-）饲喂高脂肪饮食。通过qRT-PCR、Western blotting和免疫荧光技术评估脂肪组织中的分子变化和过氧化物酶体丰度。Pex11a（-/-）显示脂肪量增加，骨骼肌减少，胆固醇水平升高，葡萄糖和胰岛素耐受性更严重受损。Pex11a（-/-）消耗的氧气较少，表明脂肪酸氧化减少，这与超长和长链脂肪酸的积累是一致的。脂肪棕榈酸（C16:0）水平在Pex11a（-/-）中升高，这可能是由于脂肪酸合成酶mRNA和蛋白质水平显著升高。此外，Pex11a缺乏增加了心室大小和巨噬细胞浸润，这与身体活动减少有关。这些数据表明，Pex11a缺乏会损害身体活动和能量消耗，减少脂肪酸β -氧化，增加新生脂肪生成，导致血脂异常和肥胖。
Peroxisomes play a central role in lipid metabolism. We previously demonstrated that Pex11a deficiency impairs peroxisome abundance and fatty acid beta-oxidation and results in hepatic triglyceride accumulation. The role of Pex11a in dyslipidaemia and obesity is investigated here with Pex11a knockout mice (Pex11a(-/-)). Metabolic phenotypes including tissue weight, glucose tolerance, insulin sensitivity, cholesterol levels, fatty acid profile, oxygen consumption, physical activity were assessed in wild-type (WT) and Pex11a(-/-) fed with a high-fat diet. Molecular changes and peroxisome abundance in adipose tissue were evaluated through qRT-PCR, Western blotting, and Immunofluorescence. Pex11a(-/-) showed increased fat mass, decreased skeletal muscle, higher cholesterol levels, and more severely impaired glucose and insulin tolerance. Pex11a(-/-) consumed less oxygen, indicating a decrease in fatty acid oxidation, which is consistent with the accumulation of very long- and long-chain fatty acids. Adipose palmitic acid (C16:0) levels were elevated in Pex11a(-/-), which may be because of dramatically increased fatty acid synthase mRNA and protein levels. Furthermore, Pex11a deficiency increased ventricle size and macrophage infiltration, which are related to the reduced physical activity. These data demonstrate that Pex11a deficiency impairs physical activity and energy expenditure, decreases fatty acid beta-oxidation, increases de novo lipogenesis and results in dyslipidaemia and obesity.