Identification of Metabolically Distinct Adipocyte Progenitor Cells in Human Adipose Tissues

• Published in: Cell reports (Cambridge) 2019-04, Vol.27 (5), p.1528-1540.e7
• Main Authors: Raajendiran, Arthe, Ooi, Geraldine, Bayliss, Jackie, O’Brien, Paul E., Schittenhelm, Ralf B., Clark, Ashlee K., Taylor, Renea A., Rodeheffer, Matthew S., Burton, Paul R., Watt, Matthew J.
• Format: Article
• Language: English
• Subjects: adipocyte progenitor cell; adipogenesis; adipokine; adipose tissue; beige adipocyte; lipid metabolism; lipolysis; obesity; type 2 diabetes
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2019.04.010

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. [Display omitted] •Identification of three distinct human adipocyte progenitor cell (APC) subtypes•APC subtypes have unique molecular profiles but similar adipogenic capacities•Adipocytes from APC subtypes have distinguishing metabolic and endocrine profiles•APC composition varies according to anatomical location and type 2 diabetes status Raajendiran et al. report the identification of three adipocyte progenitor cell (APC) subtypes that reside in human adipose tissues. These APCs have distinct molecular phenotypes yet retain similar adipogenic potential. The APCs give rise to adipocytes with divergent metabolic and endocrine capacities and their distribution varies in type 2 diabetes patients.