Obesity of mice lacking VAP-1/SSAO by Aoc3 gene deletion is reproduced in mice expressing a mutated vascular adhesion protein-1 (VAP-1) devoid of amine oxidase activity

Hypercholesterolemia of obese mice with deletion of vascular adhesion protein-1 occurs without other atherosclerosis risk factor

“…These findings are in line with the already reported lack of amine oxidase activity in AOC3KO mice [3,4] . In these previous studies, the amine oxidase activity was expressed per milligram of protein, as is usual for enzymatic activity.…”

“…Indeed, most of the CD45 + cells were located within the vessels irrigating the fat depot, suggesting that the extravasation of leukocytes was limited under Aoc3 targeted deletion. This observation was in line with the previously reported lower expression of the pan-leukocyte marker CD45 mRNA in WAT of AOC3KO mice when compared to WT [3] . Additionally, the apparent cell size of the adipocytes was larger in AOC3KO than in WT mice, a qualitative observation that was not quantified [Figure 3] but agreed with the previously reported excessive fattening of AOC3KO mice [3,4] .…”

“…This observation was in line with the previously reported lower expression of the pan-leukocyte marker CD45 mRNA in WAT of AOC3KO mice when compared to WT [3] . Additionally, the apparent cell size of the adipocytes was larger in AOC3KO than in WT mice, a qualitative observation that was not quantified [Figure 3] but agreed with the previously reported excessive fattening of AOC3KO mice [3,4] . All these observations were also dealing with the overweight phenotype found for both male and female mice with null mutation of Aoc3 [Figure 4].…”

“…Mice were weighed weekly, and subgroups were randomly constituted for the determination of individual daily urine production or for glucose tolerance tests as already described [16] . At the end of this non-invasive follow-up, mice were euthanized and aorta, WAT, kidney, heart and liver were frozen for subsequent measurements or mRNA extraction as previously described [3,4] . Adipocytes were immediately isolated from intra-abdominal white adipose tissues (INWAT: perirenal plus perigonadal plus retroperitoneal fat pads) by liberase digestion for subsequent measurement of lipolytic activities or frozen for mRNA quantification or amine oxidase activity.…”

“…Indeed, WAT not only stores lipids, but it has also been reported that its secretions (adipokines and exosomes) can directly influence the pathogenesis of atherosclerosis [2] . As we previously described a mouse model developing obesity without increased signs of inflammation in WAT [3] , it appeared of interest to further investigate whether this unusual situation may influence the risk of atherosclerosis, especially when considering that this transgenic mouse model exhibits increased circulating cholesterol levels [4] . Indeed, the above-mentioned model is a mouse with total Aoc3 gene knock-out (AOC3KO), generated and characterized by the group of Salmi and Jalkanen [5] , and which we used to further explore WAT physiology [4] .…”