Granulocyte/macrophage colony-stimulating factor-dependent dendritic cells restrain lean adipose tissue expansion

Nathalie Pamir, Ning Chun Liu, Angela Irwin, Lev Becker, YuFeng Peng, Graziella E. Ronsein, Karin E. Bornfeldt, Jeremy S. Duffield, Jay W. Heinecke

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 colonystimulating 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.

Original languageEnglish (US)
Pages (from-to)14656-14667
Number of pages12
JournalJournal of Biological Chemistry
Volume290
Issue number23
DOIs
StatePublished - Jun 5 2015
Externally publishedYes

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Tissue Expansion
Granulocyte-Macrophage Colony-Stimulating Factor
Dendritic Cells
Adipose Tissue
Tissue
Macrophages
Adipocytes
Matrix Metalloproteinase 12
Adipogenesis
White Adipose Tissue
Conditioned Culture Medium
Lipids
Fibronectins
Granulocytes
Tissue homeostasis
Fat-Restricted Diet
Adiposity
Nutrition
Proteomics
Bone

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Granulocyte/macrophage colony-stimulating factor-dependent dendritic cells restrain lean adipose tissue expansion. / Pamir, Nathalie; Liu, Ning Chun; Irwin, Angela; Becker, Lev; Peng, YuFeng; Ronsein, Graziella E.; Bornfeldt, Karin E.; Duffield, Jeremy S.; Heinecke, Jay W.

In: Journal of Biological Chemistry, Vol. 290, No. 23, 05.06.2015, p. 14656-14667.

Research output: Contribution to journalArticle

Pamir, N, Liu, NC, Irwin, A, Becker, L, Peng, Y, Ronsein, GE, Bornfeldt, KE, Duffield, JS & Heinecke, JW 2015, 'Granulocyte/macrophage colony-stimulating factor-dependent dendritic cells restrain lean adipose tissue expansion', Journal of Biological Chemistry, vol. 290, no. 23, pp. 14656-14667. https://doi.org/10.1074/jbc.M115.645820
Pamir, Nathalie ; Liu, Ning Chun ; Irwin, Angela ; Becker, Lev ; Peng, YuFeng ; Ronsein, Graziella E. ; Bornfeldt, Karin E. ; Duffield, Jeremy S. ; Heinecke, Jay W. / Granulocyte/macrophage colony-stimulating factor-dependent dendritic cells restrain lean adipose tissue expansion. In: Journal of Biological Chemistry. 2015 ; Vol. 290, No. 23. pp. 14656-14667.
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