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Cell Rep. 2019 Apr 30;27(5):1528-1540.e7. doi: 10.1016/j.celrep.2019.04.010.

Identification of Metabolically Distinct Adipocyte Progenitor Cells in Human Adipose Tissues.

Author information

1
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.
2
Centre for Obesity Research and Education, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC 3004, Australia.
3
Department of Physiology, The University of Melbourne, Melbourne, VIC 3010, Australia.
4
Monash Biomedical Proteomics Facility and Department of Biochemistry and Molecular Biology, Wellington Road, Monash University, Clayton, VIC 3800, Australia.
5
Cancer Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC 3800, Australia.
6
Department of Physiology, Monash University, Clayton, VIC 3800, Australia; Cancer Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia.
7
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.
8
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. Electronic address: matt.watt@unimelb.edu.au.

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.

KEYWORDS:

adipocyte progenitor cell; adipogenesis; adipokine; adipose tissue; beige adipocyte; lipid metabolism; lipolysis; obesity; type 2 diabetes

PMID:
31042478
DOI:
10.1016/j.celrep.2019.04.010
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