Identification of Metabolically Distinct Adipocyte Progenitor Cells in Human Adipose Tissues

Arthe Raajendiran,Geraldine Ooi,Jackie Bayliss,Paul E O’Brien,Ralf B Schittenhelm,Ashlee K Clark,Renea A Taylor,Matthew S Rodeheffer,Paul R Burton,Matthew J Watt

doi:10.1016/j.celrep.2019.04.010

Arthe Raajendiran, Geraldine Ooi + Show 8 more

Open Access

https://doi.org/10.1016/j.celrep.2019.04.010

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Abstract

Adipocyte progenitor cells (APCs) provide the reservoir of regenerative cells to produce new adipocytes, although their identity in humans remains elusive. Using FACS analysis, gene expression profiling, and metabolic and proteomic analyses, we identified three APC subtypes in human white adipose tissues. The APC subtypes are molecularly distinct but possess similar proliferative and adipogenic capacities. Adipocytes derived from APCs with high CD34 expression exhibit exceedingly high rates of lipid flux compared with APCs with low or no CD34 expression, while adipocytes produced from CD34- APCs display beige-like adipocyte properties and a unique endocrine profile. APCs were more abundant in gluteofemoral compared with abdominal subcutaneous and omental adipose tissues, and the distribution of APC subtypes varies between depots and in patients with type 2 diabetes. These findings provide a mechanistic explanation for the heterogeneity of human white adipose tissue and a potential basis for dysregulated adipocyte function in type 2 diabetes.

Highlights

The major function of adipose tissue is to maintain systemic energy balance through the storage and release of free fatty acids and via the secretion of adipokines, which communicate locally and with other organs to regulate food intake, energy expenditure, and a myriad of metabolic processes (Rosen and Spiegelman, 2014)
New adipocytes are derived from the proliferation and differentiation of preadipocytes or adipocyte progenitor cells (APCs), which reside within the stromal vascular fraction of adipose tissue
Several cell surface proteins are commonly reported to be expressed on stromal vascular fraction cells that can undergo adipogenesis (e.g., CD34, CD29, CD13, CD44, CD73, CD90, CD142, and CD9); there is no consensus on the molecular, metabolic, and endocrine profiles of adipocytes derived from specific human APC populations (Cawthorn et al, 2012)

Summary

Introduction

The major function of adipose tissue is to maintain systemic energy balance through the storage and release of free fatty acids and via the secretion of adipokines, which communicate locally and with other organs to regulate food intake, energy expenditure, and a myriad of metabolic processes (Rosen and Spiegelman, 2014). While the precise origin of the APCs is unresolved (Berry et al, 2014b), prospective approaches have established CD31À, CD45À, CD29+, CD34+, Sca-1+, and CD24+ (or CD24À) cells as committed murine white adipocyte progenitors capable of adipogenesis (Berry and Rodeheffer, 2013; Macotela et al, 2012; Rodeheffer et al, 2008). Transplantation of these cells into the primordial fat cavity of lipodystrophic mice formed a viable white adipose tissue depot and rescued the diabetic phenotype of these mice (Rodeheffer et al, 2008). Several cell surface proteins are commonly reported to be expressed on stromal vascular fraction cells that can undergo adipogenesis (e.g., CD34, CD29, CD13, CD44, CD73, CD90, CD142, and CD9); there is no consensus on the molecular, metabolic, and endocrine profiles of adipocytes derived from specific human APC populations (Cawthorn et al, 2012)

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Discussion

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