Semicarbazide-Sensitive Amine Oxidase/Vascular Adhesion Protein-1 Deficiency Reduces Leukocyte Infiltration into Adipose Tissue and Favors Fat Deposition

Abstract

Obesity is associated with low-grade inflammation and leukocyte infiltration in white adipose tissue (WAT) and is linked to diabetic complications. Semicarbazide-sensitive amine oxidase, also known as vascular adhesion protein-1 (SSAO/VAP-1), is a membrane protein that is highly expressed in adipocytes and is also present on the endothelial cell surface where it is involved in leukocyte extravasation. We studied fat deposition and leukocyte infiltration in WAT of mice with a null mutation in the amine oxidase coppercontaining-3 (AOC3) gene encoding SSAO/VAP-1. Both epididymal and inguinal WATs were larger in 6-monthold AOC3-KO males than in age-matched wild-type controls. However, WAT from AOC3-KO mice contained lower CD45 mRNA levels and fewer CD45 ؉ leukocytes. Subpopulation analyses revealed a diminished infiltration of WAT by T cells, macrophages, natural killer, and natural killer T cells. A decrease in leukocyte content

Immuno-metabolism and adipose tissue: The key role of hematopoietic stem cells

“…This ability of BM-HSC to generate WAT immune cells has been demonstrated by injecting BM cells into lethally irradiated mice, suggesting that hematopoietic cells present in WAT are derived from BM [7,8,76]. However, several observations can challenge this view.…”

Vascular adhesion protein-1 promotes liver inflammation and drives hepatic fibrosis

“…VAP-1 substrates have been shown to activate glucose transport (59), and feeding mice the SSAO inhibitor semicarbazide limits weight gain and inhibits fat deposition in adipose tissue (60). However, Bour et al demonstrated that Aoc3 -/-animals have reduced leukocyte infiltration into white adipose tissue associated with increased fat deposition, which could not be rescued by expression of VAP-1 from the human adipocyte-specific aP2 promoter (61). These data suggest that the role of VAP-1 in the development of hepatic steatosis is complex and that the effects of adipocyte-specific VAP-1 on the release of adipokines must also be taken into consideration.…”

In situ production of innate immune cells in murine white adipose tissue

“…In most cases, these immune cells come from other sites, probably the BM via blood circulation. [3][4] Several years ago, we proposed that a population of immature hematopoietic cells able to reconstitute lethally irradiated mice are located in WAT. 5 This hypothesis is consistent with a recent report demonstrating that the bulk of stroma cells host immature hematopoietic cells.…”