Developmental and functional heterogeneity of white adipocytes within a single fat depot

EMBO J. 2019 Feb 1;38(3):e99291. doi: 10.15252/embj.201899291. Epub 2018 Dec 10.

Abstract

Recent studies suggest that, even within a single adipose depot, there may be distinct subpopulations of adipocytes. To investigate this cellular heterogeneity, we have developed multiple conditionally immortalized clonal preadipocyte lines from white adipose tissue of mice. Analysis of these clones reveals at least three white adipocyte subpopulations. These subpopulations have differences in metabolism and differentially respond to inflammatory cytokines, insulin, and growth hormones. These also have distinct gene expression profiles and can be tracked by differential expression of three marker genes: Wilms' tumor 1, transgelin, and myxovirus 1. Lineage tracing analysis with dual-fluorescent reporter mice indicates that these adipocyte subpopulations have differences in gene expression and metabolism that mirror those observed in the clonal cell lines. Furthermore, preadipocytes and adipocytes from these subpopulations differ in their abundance in different fat depots. Thus, white adipose tissue, even in a single depot, is comprised of distinct subpopulations of white adipocytes with different physiological phenotypes. These differences in adipocyte composition may contribute to the differences in metabolic behavior and physiology of different fat depots.

Keywords: adipose tissue; development; lineage tracing; metabolic syndrome; obesity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes, White / classification*
  • Adipocytes, White / cytology*
  • Adipocytes, White / physiology
  • Adipogenesis*
  • Adipose Tissue / cytology*
  • Adipose Tissue / physiology
  • Animals
  • Biomarkers / analysis*
  • Cytokines / metabolism
  • Energy Metabolism
  • Human Growth Hormone / metabolism
  • Inflammation Mediators / metabolism
  • Insulin / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Microfilament Proteins / metabolism
  • Muscle Proteins / metabolism
  • Repressor Proteins / metabolism
  • Transcriptome
  • WT1 Proteins

Substances

  • Biomarkers
  • Cytokines
  • Inflammation Mediators
  • Insulin
  • Microfilament Proteins
  • Muscle Proteins
  • Repressor Proteins
  • Tagln protein, mouse
  • WT1 Proteins
  • WT1 protein, mouse
  • Human Growth Hormone