CD36 deletion reduces VLDL secretion, modulates liver prostaglandins, and exacerbates hepatic steatosis in ob/ob mice
CD36 deletion reduces VLDL secretion, modulates liver prostaglandins, and exacerbates hepatic steatosis in ob/ob mice
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DOI：
10.1194/jlr.m037812
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发表时间：
2013-11-01
影响因子：
6.5
通讯作者：
Abumrad, Nada A.
中科院分区：
文献类型：
--
作者：
Nassir, Fatiha;Adewole, Okunade L.;Abumrad, Nada A.
最近的研究结果描述了CD 36介导的信号传导在调节细胞钙和各种生物活性分子（包括胰高血糖素、神经递质、胆囊收缩素和胰泌素）释放中的作用。在这里，我们记录的作用，CD 36在肝脏VLDL的分泌。CD 36缺失导致体内VLDL输出的60%抑制，并且使用孵育的肝切片在体外减少VLDL分泌。CD 36缺失的作用是通过增强肝胰高血糖素D2、F2和E2的形成来介导的。用环加氧酶抑制剂处理CD 36缺陷切片逆转了甘油三酯分泌的减少。我们还研究了CD 36缺失对ob/ob小鼠肥胖相关的自发性脂肪变性的影响，该脂肪变性由增强的从头脂肪生成驱动。产生缺乏CD 36的纯合子ob/ob小鼠（ob-CD 36（-/-）），并研究肝脏甘油三酯蓄积和VLDL分泌。ob/ob小鼠的肝脏如预期的那样脂肪变性，并且在枯否细胞和肝细胞上具有5倍多的CD 36。CD 36缺失通过增加前列腺素水平损害肝脏甘油三酯和apoB分泌而加重脂肪变性。这些发现表明CD 36在调节VLDL分泌方面的作用未得到重视，这可能与某些形式的脂肪肝有关。他们提供了深入了解在人类中报道的CD 36蛋白表达与血清apoB水平和VLDL颗粒数量之间的关联。
Recent findings described the role of CD36-mediated signaling in regulating cellular calcium and the release of various bioactive molecules, including the prostaglandins, neurotransmitters, cholecystokinin, and secretin. Here we document the role of CD36 in the secretion of hepatic VLDL. CD36 deletion resulted in 60% suppression of VLDL output in vivo, and VLDL secretion was reduced in vitro using incubated liver slices. The effect of CD36 deletion was mediated by enhancing formation of hepatic prostaglandins D2, F2, and E2. Treatment of CD36-deficient slices with inhibitors of cyclooxygenases reversed the reduction in triglyceride secretion. We also examined the effect of CD36 deletion on the obesity-associated spontaneous steatosis of the ob/ob mouse that is driven by enhanced de novo lipogenesis. Homozygous ob/ob mice lacking CD36 (ob-CD36(-/-)) were generated and studied for hepatic triglyceride accumulation and VLDL secretion. Livers of ob/ob mice were steatotic as expected and had 5-fold more CD36 on Kupffer cells and hepatocytes. CD36 deletion exacerbated the steatosis by impairing hepatic triglyceride and apoB secretion through increasing prostaglandin levels. These findings suggest an unappreciated role of CD36 in regulating VLDL secretion, which might have relevance to some forms of fatty liver. They provide insight into the association reported in humans between CD36 protein expression and serum levels of apoB and VLDL particle number.