Identification of Metabolically Distinct Adipocyte Progenitor Cells in Human Adipose Tissues

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abdominal Fat / cytology*
  • Abdominal Fat / pathology
  • Adipocytes / classification
  • Adipocytes / metabolism*
  • Adipocytes / physiology
  • Adiposity
  • Adult
  • Animals
  • Antigens, CD34 / genetics
  • Antigens, CD34 / metabolism
  • Cell Proliferation
  • Cells, Cultured
  • Diabetes Mellitus, Type 2 / pathology*
  • Female
  • Humans
  • Male
  • Mesenchymal Stem Cells / classification
  • Mesenchymal Stem Cells / metabolism*
  • Mesenchymal Stem Cells / physiology
  • Mice
  • Mice, SCID
  • Middle Aged
  • Proteome
  • Subcutaneous Fat / cytology*
  • Subcutaneous Fat / pathology
  • Transcriptome

Substances

  • Antigens, CD34
  • Proteome