Novel Pathway of Adipogenesis through Cross-Talk between Adipose Tissue Macrophages, Adipose Stem Cells and Adipocytes: Evidence of Cell Plasticity
Simmons, Charles F.
Dumesic, Daniel A.
MetadataShow full item record
AbstractIntroduction: Previous studies highlight a complex relationship between lineage and phenotype for adipose tissue macrophages (ATMs), adipose stem cells (ASCs), and adipocytes, suggesting a high degree of plasticity of these cells. In the present study, using a novel co-culture system, we further characterized the interaction between ATMs, ASCs and adipocytes.
Research Design and Methods: Human adipocytes and the stromal vascular fraction containing ATMs and ASCs were isolated from human adipose tissue and co-cultured for 24 hours. FACS was used to characterize ATMs and ASCs before and after co-culture. Preadipocytes generated after co-culture were characterized by immunostaining for DLK (preadipocytes), CD14 and CD68 (ATMs), CD34 (ASCs), and Nile Red staining for lipid drops. qRT-PCR was used to quantify adipogenic markers such as C/EBPa and PPARc. A novel fluorescent nanobead lineage tracing method was utilized before co-culture where fluorescent nanobeads were internalized by CD68 (+) ATMs.
Results: Co-culture of adipocytes with ATMs and ASCs increased the formation of new preadipocytes, thereby increasing lipid accumulation and C/EBPa and PPARc gene expression. Preadipocytes originating after co-culture were positive for markers of preadipocytes, ATMs and ASCs. Moreover, fluorescent nanobeads were internalized by ATMs before co-culture and the new preadipocytes formed after co-culture also contained fluorescent nanobeads, suggesting that new preadipocytes originated in part from ATMs. The formation of CD34(+)/CD68(+)/DLK (+) cell spheres supported the interaction of ATMs, ASCs and preadipocytes.
Conclusions: Cross-talk between adipocytes, ATMs and ASCs promotes preadipocyte formation. The regulation of this novel adipogenic pathway involves differentiation of ATMs to preadipocytes. The presence of CD34(+)/CD68(+)/DLK(+) cells grouped in spheres suggest that paracrine interactions between these cell types plays an important role in the generation and proliferation of new preadipocytes. This phenomenon may reflect the in vivo plasticity of adipose tissue in which ATMs play an additional role during inflammation and other disease states. Understanding this novel pathway could influence adipogenesis, leading to new treatments for obesity, inflammation, and type 2 diabetes.
CitationPLoS One. 2011 Mar 31; 6(3):e17834
- MicroRNA-10a-5p regulates macrophage polarization and promotes therapeutic adipose tissue remodeling.
- Authors: Cho YK, Son Y, Kim SN, Song HD, Kim M, Park JH, Jung YS, Ahn SY, Saha A, Granneman JG, Lee YH
- Issue date: 2019 Nov
- Adipogenesis induced by human adipose tissue-derived stem cells.
- Authors: Tsuji W, Inamoto T, Yamashiro H, Ueno T, Kato H, Kimura Y, Tabata Y, Toi M
- Issue date: 2009 Jan
- Characterization of human adipose tissue-resident hematopoietic cell populations reveals a novel macrophage subpopulation with CD34 expression and mesenchymal multipotency.
- Authors: Eto H, Ishimine H, Kinoshita K, Watanabe-Susaki K, Kato H, Doi K, Kuno S, Kurisaki A, Yoshimura K
- Issue date: 2013 Mar 15
- Macrophage-secreted factors impair human adipogenesis: involvement of proinflammatory state in preadipocytes.
- Authors: Lacasa D, Taleb S, Keophiphath M, Miranville A, Clement K
- Issue date: 2007 Feb
- Notch3 is involved in adipogenesis of human adipose-derived stromal/stem cells.
- Authors: Sandel DA, Liu M, Ogbonnaya N, Newman JJ
- Issue date: 2018 Jul