title: Involvement of mast cells in adipose tissue fibrosis.
abstract: Recently, fibrosis is observed in obese adipose tissue; however, the pathogenesis remains to be clarified. Obese adipose tissue is characterized by chronic inflammation with massive accumulation of immune cells including mast cells. The objective of the present study was to clarify the relationship between fibrosis and mast cells in obese adipose tissue, as well as to determine the origin of infiltrating mast cells. We observed the enhancement of mast cell accumulation and fibrosis in adipose tissue of severely obese diabetic db/db mice. Furthermore, adipose tissue-conditioned medium (ATCM) from severely obese diabetic db/db mice significantly enhanced collagen 5 mRNA expression in NIH-3T3 fibroblasts, and this enhancement was suppressed by the addition of an anti-mast cell protease 6 (MCP-6) antibody. An in vitro study showed that only collagen V among various types of collagen inhibited preadipocyte differentiation. Moreover, we found that ATCM from the nonobese but not obese stages of db/db mice significantly enhanced the migration of bone marrow-derived mast cells (BMMCs). These findings suggest that immature mast cells that infiltrate into adipose tissue at the nonobese stage gradually mature with the progression of obesity and diabetes and that MCP-6 secreted from mature mast cells induces collagen V expression in obese adipose tissue, which may contribute to the process of adipose tissue fibrosis. Induction of collagen V by MCP-6 might accelerate insulin resistance via the suppression of preadipocyte differentiation.
authors: Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, Japan;
authors: Shizuka
authors: S
authors: Hirai
authors: Chie
authors: C
authors: Ohyane
authors: Young-Il
authors: YI
authors: Kim
authors: Shan
authors: S
authors: Lin
authors: Tsuyoshi
authors: T
authors: Goto
authors: Nobuyuki
authors: N
authors: Takahashi
authors: Chu-Sook
authors: CS
authors: Kim
authors: Jihey
authors: J
authors: Kang
authors: Rina
authors: R
authors: Yu
authors: Teruo
authors: T
authors: Kawada
mesh_terms: D041721:3T3-L1 Cells; D000273:Adipose Tissue / Q000276:immunology / Q000473:pathology*; D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology; D002465:Cell Movement; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000473:pathology; D005355:Fibrosis; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D041681:NIH 3T3 Cells
keywords: MCP-6; adipose tissue; fibrosis; mast cell; obesity