Department of Molecular and Life Sciences, College of Science and Technology, Hanyang University (ERICA campus), Ansan, Korea.
Department of Neurology, Dankook University Hospital, Cheonan, Chungnam, Korea.
Pharmacol Rep. 2017 Dec;69(6):1140-1144. doi: 10.1016/j.pharep.2017.05.019. Epub 2017 Jun 4.
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.
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.
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.
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.
最近，开发了一种肽疫苗（B4T），可预防野生型小鼠高脂肪饮食（HFD）诱导的肥胖和肝脂肪变性，并且似乎针对载脂蛋白 B100 中的表位，但不针对载脂蛋白 B48。在这里，我们询问 B4T 在载脂蛋白 E 敲除（ApoE-ko）小鼠中是否仍然有效，ApoE-ko 小鼠表现出载脂蛋白 B48/载脂蛋白 B100 比值大大增加，并在 HFD 下发生动脉粥样硬化。
在 5 至 15 周龄之间，HFD 喂养的雄性 ApoE-ko 小鼠接受 B4T 或载体注射 3 次。直到 45 周龄，定期测量体重并确定抗体滴度。最后，检查肥胖症和器官组织学。
我们发现，在 ApoE-ko 小鼠中，B4T 可防止 HFD 诱导的体重增加（p<0.01），其程度与以前在野生型小鼠中观察到的相当。此外，如以前在野生型小鼠中观察到的那样，还可以预防肝脂肪变性。相比之下，在研究的任何接种疫苗的小鼠中均未预防动脉粥样硬化斑块形成，这与抗体产生与体重减轻平行但在动脉粥样硬化形成之前很大程度上平行的观察结果一致。
这些发现表明，尽管 ApoB48/B100 比值增加，但 B4T 仍然有效，但对新形成的斑块形成没有影响。至少在当前的疫苗接种方案下，载脂蛋白 B 的肥胖和动脉粥样硬化相关作用似乎是可分离的。
