Identification of a Paracrine Signaling Mechanism Linking CD34high Progenitors to the Regulation of Visceral Fat Expansion and Remodeling

Cell Rep. 2019 Oct 8;29(2):270-282.e5. doi: 10.1016/j.celrep.2019.08.092.

Abstract

Accumulation of visceral (VIS) is a predictor of metabolic disorders and insulin resistance. This is due in part to the limited capacity of VIS fat to buffer lipids allowing them to deposit in insulin-sensitive tissues. Mechanisms underlying selective hypertrophic growth and tissue remodeling properties of VIS fat are not well understood. We identified subsets of adipose progenitors (APs) unique to VIS fat with differential Cd34 expression and adipogenic capacity. VIS low (Cd34 low) APs are adipogenic, whereas VIS high (Cd34 high) APs are not. Furthermore, VIS high APs inhibit adipogenic differentiation of SUB and VIS low APs in vitro through the secretion of soluble inhibitory factor(s). The number of VIS high APs increased with adipose tissue expansion, and their abundance in vivo caused hypertrophic growth, fibrosis, inflammation, and metabolic dysfunction. This study unveils the presence of APs unique to VIS fat involved in the paracrine regulation of adipogenesis and tissue remodeling.

Keywords: adipose progenitors; cell sorting; fat expansion; transplantation; visceral fat.

Publication types

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

MeSH terms

  • Adipogenesis / drug effects
  • Adipose Tissue, White / cytology
  • Animals
  • Antigens, CD34 / metabolism*
  • Bone Morphogenetic Protein 4 / pharmacology
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Insulin Resistance
  • Intra-Abdominal Fat / cytology*
  • Intra-Abdominal Fat / metabolism
  • Male
  • Mice, Inbred C57BL
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / metabolism
  • Paracrine Communication* / drug effects
  • Phenotype
  • Rosiglitazone / pharmacology
  • Signal Transduction* / drug effects
  • Solubility
  • Stem Cells / drug effects
  • Stem Cells / metabolism*
  • Weight Gain / drug effects

Substances

  • Antigens, CD34
  • Bone Morphogenetic Protein 4
  • Rosiglitazone