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Reducing 14-3-3ζ expression influences adipocyte maturity and impairs function.

Abel K Oppong1,2, Kadidia Diallo1,2, Isabelle Robillard Frayne3

  • 1Department of Medicine, Université de Montréal, Montreal, Quebec, Canada.

American Journal of Physiology. Endocrinology and Metabolism
|May 6, 2020
PubMed
Summary

14-3-3ζ protein is essential for mature adipocyte function, regulating lipolysis and maintaining adipocyte maturity. Depleting 14-3-3ζ impairs lipid breakdown and adipocyte differentiation.

Keywords:
14-3-3ζadipocyteheterogeneitylipolysismaturityscaffold proteins

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Area of Science:

  • Metabolic regulation
  • Cellular biology
  • Molecular signaling

Background:

  • Mature adipocytes supply energy through lipolysis, involving enzymes like adipose triacylglycerol lipase (ATGL) and hormone-sensitive lipase (HSL).
  • Phosphorylation of ATGL and HSL creates binding sites for 14-3-3 proteins, suggesting a role in lipolysis.
  • Previous work highlighted 14-3-3ζ's role in adipogenesis, but its function in mature adipocytes was unclear.

Purpose of the Study:

  • To investigate the role of 14-3-3ζ in lipolysis and adipocyte maturity.
  • To determine the impact of 14-3-3ζ depletion on adipocyte-specific functions.

Main Methods:

  • Depletion of 14-3-3ζ in male mice and 3T3-L1 adipocytes.
  • Measurement of glycerol and free fatty acid (FFA) release.
  • Analysis of peroxisome proliferator-activated receptor (PPAR)γ2 protein abundance and gene expression.
  • Untargeted lipidomics to assess adipocyte lipid profiles.

Main Results:

  • 14-3-3ζ depletion significantly impaired lipolysis, reducing glycerol and FFA release.
  • Reduced 14-3-3ζ expression negatively affected adipocyte maturity, indicated by decreased PPARγ2 and mature adipocyte gene expression.
  • Lipidomic analysis revealed that 14-3-3ζ-deficient adipocytes exhibited a lipid profile similar to undifferentiated preadipocytes.

Conclusions:

  • 14-3-3ζ is crucial for maintaining adipocyte maturity and function, including lipolysis.
  • The study uncovers a novel role for 14-3-3ζ in regulating adipocyte-specific processes.
  • Impaired 14-3-3ζ abundance negatively impacts adipocyte lipid metabolism and differentiation status.