An ApoB100-mimetic vaccine prevents obesity and liver steatosis in ApoE-/- mice
An ApoB100-mimetic vaccine prevents obesity and liver steatosis in ApoE-/- mice
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DOI：
10.1016/j.pharep.2017.05.019
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发表时间：
2017-12-01
影响因子：
4.4
通讯作者：
Kim, Hyo Joon
中科院分区：
文献类型：
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作者：
Kong, Su-Kang;Choe, Moon Kyung;Kim, Hyo Joon
背景：最近，一种肽疫苗（B4T）被开发出来，可以预防高脂肪饮食（HFD）诱导的野生型小鼠肥胖和肝脏脂肪变性，并且似乎靶向存在于ApoB100而不是ApoB48中的表位。在这里，我们询问B4T是否在ApoE敲除（ApoE-ko）小鼠中仍然有效，这些小鼠在HFD下表现出ApoB48/ApoB100比率大幅增加并发生动脉粥样硬化。方法：饲喂hfd的雄性ApoE-ko小鼠，在5 ~ 15周龄注射B4T或载药3次。直到45周龄，他们定期称重并测定抗体滴度。最后进行脂肪和器官组织学检查。结果：我们发现，在ApoE-ko小鼠中，B4T可以阻止hfd诱导的体重增加（p < 0.01），其程度与之前在野生型小鼠中显示的相当。此外，正如先前在野生型小鼠中所显示的那样，肝脏脂肪变性也得到了预防。相比之下，在任何接种疫苗的小鼠中，动脉粥样硬化斑块的形成都没有被阻止，这与抗体的产生与体重减轻并行，但在很大程度上先于动脉粥样硬化形成的观察结果一致。结论：研究结果表明，尽管ApoB48/B100比值增加，但B4T对新生斑块形成的影响并不明显。至少在目前的疫苗接种计划下，ApoB与肥胖和动脉粥样硬化相关的作用似乎是可分离的。(c) 2017年波兰科学院药理学研究所。Elsevier Sp. zo.o出版，版权所有。
Background: Recently, a peptide vaccine (B4T) was developed that prevents high fat diet (HFD)-induced obesity and liver steatosis in wild type mice and appears to target an epitope present in ApoB100 but not ApoB48. Here, we ask whether B4T remains effective in ApoE knockout (ApoE-ko) mice, which exhibit a greatly increased ApoB48/ApoB100 ratio and develop atherosclerosis under HFD.Methods: HFD-fed male ApoE-ko mice were injected with B4T or vehicle 3 times between 5 and 15 weeks of age. Until 45 weeks of age, they were regularly weighed and antibody titers determined. In the end, adiposity and organ histologies were examined.Results: We find that in the ApoE-ko mice, B4T prevents HFD-induced body weight increases (p < 0.01) to a comparable degree as previously shown in wild type mice. Also, liver steatosis was prevented as previously shown in wild type mice. By contrast, atherosclerotic plaque formation was not prevented in any of the vaccinated mice studied, in line with the observation that antibody production paralleled the weight reduction but largely preceded atherogenesis.Conclusion: The findings demonstrate effectiveness of B4T despite the increased ApoB48/B100 ratio, but argue against an effect on de novo plaque formation. At least under the current vaccination schedule, the obesity-and atherosclerosis-related roles of ApoB appear to be dissociable. (c) 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Sp. z o.o. All rights reserved.