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Sprouty1 regulates gonadal white adipose tissue growth through a PDGFRα/β-Akt pathway

Xuehui Yang1, Shivangi Pande1,2, Robert A Koza1,2

  • 1Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, ME, USA.

Adipocyte
|October 29, 2021
PubMed

Insights

SPRY1 protein deficiency causes excessive growth in mouse gonadal white adipose tissue (gWAT) by promoting adipocyte progenitor cell proliferation and differentiation. This highlights SPRY1

Area of Science:

  • Adipose tissue biology
  • Metabolic disease research
  • Cell signaling pathways

Background:

  • Visceral white adipose tissue (vWAT) expansion is linked to metabolic disease risk.
  • SPRY1, a receptor tyrosine kinase (RTK) signaling inhibitor, is present in adipocyte progenitor cells (APCs).

Purpose of the Study:

  • To investigate the role of SPRY1 in regulating visceral white adipose tissue (vWAT) growth.
  • To determine the impact of SPRY1 deficiency on adipocyte progenitor cell (APC) proliferation and differentiation.

Main Methods:

  • Utilized global Spry1 knockout (Spry1KO) mice and wild-type (WT) littermates.
  • Analyzed gonadal WAT (gWAT) for cell proliferation, fibrosis, inflammation, and collagen deposition.
  • Performed in vitro studies on stromal vascular fraction (SVF) cells to assess adipocyte differentiation and signaling pathways (PDGF, AKT).

Main Results:

  • Spry1KO mice exhibited disproportionate postnatal growth of gWAT compared to WT mice.
  • Spry1 deficiency led to increased PDGFRa+ APCs, proliferation, fibrosis, collagen deposition, and inflammation markers in gWAT.
  • SPRY1 deficiency enhanced PDGF-AA/BB-induced SVF cell proliferation and AKT activation; PDGF-BB sustained SPRY1 downregulation.

Conclusions:

  • SPRY1 is crucial for controlling postnatal gWAT growth by limiting APC proliferation and differentiation.
  • SPRY1 regulates PDGFRa/b-AKT signaling, impacting adipose tissue expansion.
  • Targeting SPRY1 may offer therapeutic strategies for metabolic diseases associated with vWAT expansion.
Keywords:
AdipocyteSprouty1cell signallingdifferentiationfibrosisproliferation

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