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
Affiliations
Arthe Raajendiran
Department of Physiology, The University of Melbourne, Melbourne, VIC 3010, Australia; Department of Physiology, Monash University, Clayton, VIC 3800, Australia; Metabolism, Diabetes and Obesity Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia
Geraldine Ooi
Centre for Obesity Research and Education, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC 3004, Australia
Jackie Bayliss
Department of Physiology, The University of Melbourne, Melbourne, VIC 3010, Australia
Paul E. O’Brien
Centre for Obesity Research and Education, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC 3004, Australia
Ralf B. Schittenhelm
Monash Biomedical Proteomics Facility and Department of Biochemistry and Molecular Biology, Wellington Road, Monash University, Clayton, VIC 3800, Australia
Ashlee K. Clark
Cancer Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC 3800, Australia
Renea A. Taylor
Department of Physiology, Monash University, Clayton, VIC 3800, Australia; Cancer Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia
Matthew S. Rodeheffer
Department of Molecular Cell and Developmental Biology; Program in Integrative Cell Signaling and Neurobiology of Metabolism, Department of Comparative Medicine; and Yale Stem Cell Center, Yale University, New Haven, CT, USA
Paul R. Burton
Centre for Obesity Research and Education, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC 3004, Australia
Matthew J. Watt
Department of Physiology, The University of Melbourne, Melbourne, VIC 3010, Australia; Department of Physiology, Monash University, Clayton, VIC 3800, Australia; Metabolism, Diabetes and Obesity Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; Corresponding author
Summary: 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. : 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. Keywords: adipose tissue, lipid metabolism, adipokine, obesity, type 2 diabetes, adipogenesis, adipocyte progenitor cell, beige adipocyte, lipolysis
