Semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 deficiency reduces leukocyte infiltration into adipose tissue and favors fat deposition.
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 copper-containing-3 (AOC3) gene encoding SSAO/VAP-1. Both epididymal and inguinal WATs were larger in 6-month-old 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 in WAT was also detected in female AOC3-KO mice as early as 2 months of age, whereas increased fat mass was evident by 6 months of age. Reduced CD45(+) populations in WAT of AOC3-KO mice was not rescued by human SSAO/VAP-1 expression on adipocytes under the control of aP2, suggesting the importance of vascular AOC3 in leukocyte entrance into fat. Our results indicate that SSAO/VAP-1 is instrumental for the presence of leukocytes in WAT. Therefore, AOC3-KO mice present a unique model of mild obesity, characterized by increased WAT devoid of low-grade inflammation.
Bour
Sandy
S
INSERM U858, équipe 3, I2MR,Université Toulouse III Paul-Sabatier, CHU Rangueil, Bât. L4, BP 84225, 31432 Toulouse cedex 4, France.
Caspar-Bauguil
Sylvie
S
Iffiú-Soltész
Zsuzsa
Z
Nibbelink
Maryse
M
Cousin
Béatrice
B
Miiluniemi
Mari
M
Salmi
Marko
M
Stolen
Craig
C
Jalkanen
Sirpa
S
Casteilla
Louis
L
Pénicaud
Luc
L
Valet
Philippe
P
Carpéné
Christian
C
D000273:Adipose Tissue / Q000473:pathology / Q000502:physiology*; D006631:Amine Oxidase (Copper-Containing) / Q000172:deficiency* / Q000235:genetics*; D000818:Animals; D015815:Cell Adhesion Molecules / Q000172:deficiency* / Q000235:genetics*; D005434:Flow Cytometry; D006801:Humans; D007962:Leukocytes / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008995:Monoamine Oxidase / Q000172:deficiency*; D009765:Obesity / Q000235:genetics; D012663:Semicarbazides / Q000494:pharmacology*
D015815:Cell Adhesion Molecules; D012663:Semicarbazides; C010059:carbamylhydrazine; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing); C492678:semicarbazide-sensitive amine oxidase-vascular adhesion protein-1, mouse; D008995:Monoamine Oxidase