Granulocyte/Macrophage Colony-stimulating Factor-dependent Dendritic Cells Restrain Lean Adipose Tissue Expansion.
The physiological roles of macrophages and dendritic cells (DCs) in lean white adipose tissue homeostasis have received little attention. Because DCs are generated from bone marrow progenitors in the presence of granulocyte/macrophage colony-stimulating factor (GM-CSF), we used GM-CSF-deficient (Csf2(-/-)) mice fed a low fat diet to test the hypothesis that adipose tissue DCs regulate the development of adipose tissue. At 4 weeks of age, Csf2(-/-) mice had 75% fewer CD45(+)Cd11b(+)Cd11c(+)MHCII(+) F4/80(-) DCs in white adipose tissue than did wild-type controls. Furthermore, the Csf2(-/-) mice showed a 30% increase in whole body adiposity, which persisted to adulthood. Adipocytes from Csf2(-/-) mice were 50% larger by volume and contained higher levels of adipogenesis gene transcripts, indicating enhanced adipocyte differentiation. In contrast, adipogenesis/adipocyte lipid accumulation was inhibited when preadipocytes were co-cultured with CD45(+)Cd11b(+)Cd11c(+)MHCII(+)F4/80(-) DCs. Medium conditioned by DCs, but not by macrophages, also inhibited adipocyte lipid accumulation. Proteomic analysis revealed that matrix metalloproteinase 12 and fibronectin 1 were greatly enriched in the medium conditioned by DCs compared with that conditioned by macrophages. Silencing fibronectin or genetic deletion of matrix metalloproteinase 12 in DCs partially reversed the inhibition of adipocyte lipid accumulation. Our observations indicate that DCs residing in adipose tissue play a critical role in suppressing normal adipose tissue expansion.
From the Departments of Medicine, pamir@ohsu.edu.
Nathalie
N
Pamir
From the Departments of Medicine.
Ning-Chun
NC
Liu
From the Departments of Medicine.
Angela
A
Irwin
the Department of Pediatrics, University of Chicago, Chicago, Illinois 60637.
Lev
L
Becker
Rheumatology, and.
YuFeng
Y
Peng
From the Departments of Medicine.
Graziella E
GE
Ronsein
From the Departments of Medicine, Pathology and.
Karin E
KE
Bornfeldt
the Division of Nephrology and Lung Biology, University of Washington, Seattle, Washington 98109-8050 and.
Jeremy S
JS
Duffield
From the Departments of Medicine.
Jay W
JW
Heinecke
D041721:3T3-L1 Cells; D050156:Adipogenesis; D000273:Adipose Tissue / Q000166:cytology* / Q000378:metabolism; D000375:Aging; D000818:Animals; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D004734:Energy Metabolism; D005260:Female; D017353:Gene Deletion; D005947:Glucose / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis; D008297:Male; D053508:Matrix Metalloproteinase 12 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000166:cytology / Q000378:metabolism
D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D053508:Matrix Metalloproteinase 12; D005947:Glucose
mice, GM-CSF, dendritic cells, adipose tissue