An ApoB100-mimetic vaccine prevents obesity and liver steatosis in ApoE-/- mice

Abstract

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.