An apolipoprotein B100 mimotope prevents obesity in mice

Abstract

Immunization with an ApoB100 mimotope prevents high-fat-diet-induced obesity in mice. Antibody titres parallel the weight decrements. In vitro data implicate increased lipolysis and reduced lipoprotein uptake by adipocytes, as well as increased uptake and metabolism of native lipoprotein by macrophages.

Biphasic Production of Anti-ApoB100 Autoantibodies in Obese Humans and Mice

“…Unexpectedly, however, no reactivity was found with p45 and p240 ( Figure 1 B). Importantly, the exact same reactivity pattern was exhibited by the monoclonal antibody 22B4 ( Figure 1 B) that we had previously raised against pB1 [ 22 ]. Thus, sera from obese mice and humans contain autoantibodies directed against the ApoB100 epitope p210, and these autoantibodies also recognize the synthetic p210 mimotope pB1.…”

“…Moreover, in both species the antibody titers appear to go through a peak before reaching the morbid stage, or at least do not further increase in morbid obesity. In conjunction with our previous study demonstrating an obesity-preventing effect of a pB1-based vaccine [ 22 ], these findings (i) add obesity to the range of pathologies in which autoantibodies potentially play a protective physiological role (see Introduction) and (ii) provide support for the rationale [ 22 ] that the anti-obesity vaccination strategy that was successful in mice can be extended into humans.…”

“…Since we have previously shown that a pB1-based vaccine (which induced antibodies that reacted with p210 and ApoB100) can prevent HFD-induced obesity in mice [ 22 ], our new finding suggests that obesity-induced anti-p210 autoantibodies may blunt the weight increase in non-vaccinated mice. In this respect, it is intriguing that in both mice and humans, the antibody titers did not continuously rise with the degree of obesity but rather decreased and leveled off in morbid obesity.…”

“…For example, it was found that autoantibodies against p210, a native epitope of human ApoB100, are associated with a reduced severity of atherosclerosis in humans [ 18 , 19 ], and immunization of mice with antibodies directed against native p210 had an anti-atherogenic effect [ 20 , 21 ], raising the possibility of a similar role of the corresponding autoantibodies. We previously found that pB1, a synthetic mimotope of p210, can induce antibodies that recognize native p210 and ApoB100 and prevent diet-induced obesity in mice [ 22 ]. We therefore speculate that in analogy with the findings on atherosclerosis, certain ApoB100/p210-reactive autoantibodies may be part of an anti-obesity, rather than pathogenic, mechanism.…”

Peptides and Peptidomimetics as Potential Antiobesity Agents: Overview of Current Status

“…Endogenous peptides and peptidomimetics approaches for treating obesity [Adapted from Navab et al (9), Tschop et al (10), and Inooka et al (11); Kim et al (12); Tala et al (13)] ( Indications- Green solid arrow-activation, blue solid arrow-suppression, red dashed arrow-antagonism, and red solid arrow-block ).…”