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J Biol Chem. 2015 Jun 5;290(23):14656-67. doi: 10.1074/jbc.M115.645820. Epub 2015 Apr 30.

Granulocyte/Macrophage Colony-stimulating Factor-dependent Dendritic Cells Restrain Lean Adipose Tissue Expansion.

Author information

1
From the Departments of Medicine, pamir@ohsu.edu.
2
From the Departments of Medicine.
3
the Department of Pediatrics, University of Chicago, Chicago, Illinois 60637.
4
Rheumatology, and.
5
From the Departments of Medicine, Pathology and.
6
the Division of Nephrology and Lung Biology, University of Washington, Seattle, Washington 98109-8050 and.

Abstract

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.

KEYWORDS:

mice, GM-CSF, dendritic cells, adipose tissue

PMID:
25931125
PMCID:
PMC4505532
DOI:
10.1074/jbc.M115.645820
[Indexed for MEDLINE]
Free PMC Article

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