Although apolipoprotein B100 (ApoB100) plays a key role in peripheral fat deposition, it is not considered a suitable therapeutic target in obesity. In the present study we describe a novel ApoB100 mimotope, peptide pB1, and the use of pB1-based vaccine-like formulations (BVFs) against high-fat diet (HFD)-induced obesity. In HFD- compared with chow-fed adolescent mice, BVFs reduced the 3-month body-weight gains attributable to increased dietary fat by 44–65%, and prevented mesenteric fat accumulation and liver steatosis. The body-weight reductions paralleled the titres of pB1-reactive immunoglobulin G (IgG) antibodies, and pB1-reactive antibodies specifically recognized native ApoB100 and a synthetic peptide from the C-terminal half of ApoB100. In cultured 3T3L1 adipocytes, anti-pB1 antibodies increased lipolysis and inhibited low-density lipoprotein (LDL) uptake. In cultured RAW 264.7 macrophages, the same antibodies enhanced LDL uptake (without causing foam cell formation). These findings make ApoB100 a promising target for an immunization strategy against HFD-induced obesity.

Mycobacterium gilvum PYR-GCK, a pyrene degrading bacterium, has been the subject of functional studies aimed at elucidating mechanisms related to its outstanding pollutant bioremediation/biodegradation activities. Several studies have investigated energy production and conservation in Mycobacterium, however, they all focused on the pathogenic strains using their various hosts as induction sources. To gain greater insight into Mycobacterium energy metabolism, mRNA expression studies focused on respiratory functions were performed under two different conditions using the toxic pollutant pyrene as a test substrate and glucose as a control substrate. This was done using two transcriptomic techniques: global transcriptomic RNA-sequencing and quantitative Real-Time PCR. Growth in the presence of pyrene resulted in upregulated expression of genes associated with limited oxygen or anaerobiosis in M.gilvum PYR-GCK. Upregulated genes included succinate dehydrogenases, nitrite reductase and various electron donors including formate dehydrogenases, fumarate reductases and NADH dehydrogenases. Oxidative phosphorylation genes (with respiratory chain complexes I, III –V) were expressed at low levels compared to the genes coding for the second molecular complex in the bacterial respiratory chain (fumarate reductase); which is highly functional during microaerophilic or anaerobic bacterial growth. This study reveals a molecular adaptation to a hypoxic mode of respiration during aerobic pyrene degradation. This is likely the result of a cellular oxygen shortage resulting from exhaustion of the oxygenase enzymes required for these degradation activities in M.gilvum PYR-GCK.

Obesity is associated with autoimmunity, a phenomenon considered as harmful. Here we show that obese mice and humans produce IgG-type autoantibodies that specifically recognize apolipoprotein B-100 (ApoB100), its native epitope p210, and the synthetic p210 mimotope pB1. By contrast, antibodies against epitopes p45 and p240, which have been associated with atherosclerosis, were not detected in either the humans or mice. In a longitudinal analysis of high fat diet-fed mice, autoantibody production rose with increasing body weight, then decreased and plateaued at morbid obesity. Likewise, in a cross-sectional analysis of sera from 148 human volunteers spanning a wide BMI range and free of comorbidities, the immunoreactivity increased and then decreased with increasing BMI. Thus, the obesity-related ApoB100-specific natural autoantibodies characteristically showed the same epitope recognition, IgG-type, and biphasic serum levels in humans and mice. We previously reported that a pB1-based vaccine induces similar antibodies and can prevent obesity in mice. Therefore, our present results suggest that autoantibodies directed against native ApoB100 may mitigate obesity, and that the vaccination approach may be effective in humans.