Perilipin+ embryonic preadipocytes actively proliferate along growing vasculatures for adipose expansion

Development. 2015 Aug 1;142(15):2623-32. doi: 10.1242/dev.125336.

Abstract

Despite the growing interest in adipose tissue as a therapeutic target of metabolic diseases, the identity of adipocyte precursor cells (preadipocytes) and the formation of adipose tissue during embryonic development are still poorly understood. Here, we clarified the identity and dynamic processes of preadipocytes in mouse white adipose tissue during embryogenesis through direct examination, lineage tracing and culture systems. Surprisingly, we found that lipid-lacking but perilipin(+) or adiponectin(+) proliferating preadipocytes started to emerge at embryonic day 16.5, and these cells underwent active proliferation until birth. Moreover, these preadipocytes resided as clusters and were distributed along growing adipose vasculatures. Importantly, the embryonic preadipocytes exhibited considerable coexpression of stem cell markers, such as CD24, CD29 and PDGFRα, and a small portion of preadipocytes were derived from PDGFRβ(+) mural cells, in contrast to the adult preadipocytes present in the stromal vascular fraction. Further analyses with in vitro and ex vivo culture systems revealed a stepwise but dynamic regulation of preadipocyte formation and differentiation during prenatal adipogenesis. To conclude, we unraveled the identity and characteristics of embryonic preadipocytes, which are crucial for the formation and expansion of adipose tissue during embryogenesis.

Keywords: Adipogenesis; Adipose tissue; Angiogenesis; Preadipocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / metabolism*
  • Adipose Tissue / blood supply
  • Adipose Tissue / embryology*
  • Animals
  • Azo Compounds
  • CD24 Antigen / metabolism
  • Carrier Proteins / metabolism*
  • Cell Proliferation / physiology*
  • Colony-Forming Units Assay
  • Flow Cytometry
  • Galactosides
  • Indoles
  • Integrin beta1 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microscopy, Confocal
  • Perilipin-1
  • Phosphoproteins / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Receptor, Platelet-Derived Growth Factor alpha / metabolism
  • Statistics, Nonparametric

Substances

  • Azo Compounds
  • CD24 Antigen
  • Carrier Proteins
  • Cd24a protein, mouse
  • Galactosides
  • Indoles
  • Integrin beta1
  • Perilipin-1
  • Phosphoproteins
  • Receptor, Platelet-Derived Growth Factor alpha
  • oil red O
  • 5-bromo-4-chloro-3-indolyl beta-galactoside