Novel Pathway of Adipogenesis through Cross-Talk between Adipose Tissue Macrophages, Adipose Stem Cells and Adipocytes: Evidence of Cell Plasticity

Hdl Handle:
http://hdl.handle.net/10675.2/646
Title:
Novel Pathway of Adipogenesis through Cross-Talk between Adipose Tissue Macrophages, Adipose Stem Cells and Adipocytes: Evidence of Cell Plasticity
Authors:
Chazenbalk, Gregorio; Bertolotto, Cristina; Heneidi, Saleh; Jumabay, Medet; Trivax, Bradley; Aronowitz, Joel; Yoshimura, Kotaro; Simmons, Charles F.; Dumesic, Daniel A.; Azziz, Ricardo ( 0000-0002-3917-0483 )
Abstract:
Introduction: 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.
Citation:
PLoS One. 2011 Mar 31; 6(3):e17834
Issue Date:
31-Mar-2011
URI:
http://hdl.handle.net/10675.2/646
DOI:
10.1371/journal.pone.0017834
PubMed ID:
21483855
PubMed Central ID:
PMC3069035
Type:
Article
ISSN:
1932-6203
Appears in Collections:
Department of Obstetrics and Gynecology: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorChazenbalk, Gregorioen_US
dc.contributor.authorBertolotto, Cristinaen_US
dc.contributor.authorHeneidi, Salehen_US
dc.contributor.authorJumabay, Medeten_US
dc.contributor.authorTrivax, Bradleyen_US
dc.contributor.authorAronowitz, Joelen_US
dc.contributor.authorYoshimura, Kotaroen_US
dc.contributor.authorSimmons, Charles F.en_US
dc.contributor.authorDumesic, Daniel A.en_US
dc.contributor.authorAzziz, Ricardoen_US
dc.date.accessioned2012-10-26T16:26:58Z-
dc.date.available2012-10-26T16:26:58Z-
dc.date.issued2011-03-31en_US
dc.identifier.citationPLoS One. 2011 Mar 31; 6(3):e17834en_US
dc.identifier.issn1932-6203en_US
dc.identifier.pmid21483855en_US
dc.identifier.doi10.1371/journal.pone.0017834en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/646-
dc.description.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.en_US
dc.description.abstractResearch 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.en_US
dc.description.abstractResults: 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.en_US
dc.description.abstractConclusions: 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.en_US
dc.rightsChazenbalk et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.subjectResearch Articleen_US
dc.subjectBiologyen_US
dc.subjectAnatomy and Physiologyen_US
dc.subjectEndocrine Systemen_US
dc.subjectEndocrine Physiologyen_US
dc.subjectAutocrine Mechanismen_US
dc.subjectEndocrine Cellsen_US
dc.subjectImmune Physiologyen_US
dc.subjectImmune Cellsen_US
dc.subjectDevelopmental Biologyen_US
dc.subjectStem Cellsen_US
dc.subjectAdult Stem Cellsen_US
dc.subjectMesenchymal Stem Cellsen_US
dc.subjectImmunologyen_US
dc.subjectImmune Cellsen_US
dc.subjectMonocytesen_US
dc.titleNovel Pathway of Adipogenesis through Cross-Talk between Adipose Tissue Macrophages, Adipose Stem Cells and Adipocytes: Evidence of Cell Plasticityen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC3069035en_US
dc.contributor.corporatenameDepartment of Obstetrics and Gynecology-

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