Adipocytes and aplastic anemia: Peroxisome proliferator-activated receptor-g (PPAR-g) inhibitors attenuate bone marrow failure in an aplastic anemia mouse model but not in radiation marrow destruction

Thursday, October 11, 2012 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center, Building 45	NHLBI	IMMUNO-18

* FARE Award Winner

Authors

• K Sato
• X Feng
• J Chen
• MJ Desierto
• K Keyvanfar
• D Maride
• S Kajigaya
• NS Young

Abstract

Aplastic anemia (AA), one of the well-known bone marrow (BM) failure diseases, is characterized by a decrease in the number and function of hematopoietic stem cells (HSCs) and progenitors, and by a massive expansion of adipocytes in BM cavities. A functional role of adipocytes in AA is unclear. In this study, we demonstrate that inhibition of adipogenesis by peroxisome proliferator–activated receptor-gamma (PPAR-g) inhibitors can improve hematopoiesis in a mouse model of immune-mediated BM failure. Mice in PPAR-g inhibitor-treated groups showed higher levels of leukocytes, neutrophils, red blood cells, and platelets in peripheral blood (PB), and higher total nucleated cells and Lin- Sca1+ c-kit+ stem cells in BM than did animals in the control group. In PPAR-g inhibitor-treated groups, there was significantly less CD8+ cell infiltration in BM, suggesting that PPAR-g inhibitors might negatively affect activation of cytotoxic T cells. Both confocal microscopic imaging and HE staining of BM also showed significantly higher numbers of nucleated cells in the treated groups. This is the first report that reveals a negative role of adipocytes in immune-mediated BM failure, and this study suggests PPAR-g can be a novel therapeutic target in AA.

back to top