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Robust Differentiation of Human iPSCs into a Pure Population of Adipocytes to Study Adipocyte-Associated Disorders
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Calreticulin inhibits commitment to adipocyte differentiation.

Eva Szabo1, Yuanyuan Qiu, Shairaz Baksh

  • 1Department of Laboratory Medicine and Pathobiology, Institute of Medical Sciences, University of Toronto, Toronto, Ontario M5S 1A8, Canada.

The Journal of Cell Biology
|July 9, 2008
PubMed
Summary

Calreticulin protein regulates fat cell formation (adipogenesis). Calreticulin deficiency enhances adipogenesis by altering calcium levels and activating specific cell signaling pathways.

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Area of Science:

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Background:

  • Calreticulin is an endoplasmic reticulum (ER) protein crucial for protein folding and calcium homeostasis.
  • Adipogenesis, the process of fat cell differentiation, is a complex pathway involving numerous molecular regulators.

Purpose of the Study:

  • To investigate the role of calreticulin in modulating adipogenesis.
  • To elucidate the molecular mechanisms by which calreticulin influences fat cell differentiation.

Main Methods:

  • Utilized embryonic stem cells and 3T3-L1 preadipocytes.
  • Compared adipogenic potential in calreticulin-deficient, wild-type, and calreticulin-overexpressing cells.
  • Assessed ER lumenal calcium concentrations and the calmodulin-Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) pathway.

Main Results:

  • Calreticulin-deficient cells exhibited increased adipogenic potency compared to controls.
  • Reduced ER lumenal calcium concentration was observed in highly adipogenic calreticulin-deficient cells.
  • Upregulation of the CaMKII pathway in calreticulin-deficient cells, with CaMKII inhibition reducing adipogenesis.
  • Calreticulin negatively regulates adipogenesis via a feedback loop involving peroxisome proliferator-activated receptor gamma (PPARγ).

Conclusions:

  • Calreticulin acts as a Ca(2+)-dependent molecular switch controlling adipocyte differentiation.
  • Calreticulin inhibits adipogenesis by preventing the expression and activation of key proadipogenic transcription factors.
  • The findings reveal a novel regulatory mechanism for adipogenesis involving ER calcium and calreticulin.