Related Experiment Video

Updated: Jul 5, 2025

Measuring the Rate of Lipolysis in Ex Vivo Murine Adipose Tissue and Primary Preadipocytes Differentiated In Vitro
09:41

Measuring the Rate of Lipolysis in Ex Vivo Murine Adipose Tissue and Primary Preadipocytes Differentiated In Vitro

Published on: March 17, 2023

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p21-activated kinase 4 counteracts PKA-dependent lipolysis by phosphorylating FABP4 and HSL

Hwang Chan Yu1, Yong Geun Jeon2, Ann-Yae Na3

  • 1Department of Biochemistry and Molecular Biology, Jeonbuk National University Medical School, Jeonju, Korea.

Nature Metabolism
|January 12, 2024
PubMed

Insights

p21-activated kinase 4 (PAK4) regulates fat breakdown (lipolysis). Inhibiting PAK4 in mice reduces obesity and insulin resistance, suggesting PAK4 inhibitors as a potential obesity treatment.

Area of Science:

  • Biochemistry
  • Metabolic Diseases
  • Cellular Signaling

Background:

  • Adipose tissue lipolysis is regulated by cAMP-protein kinase A (PKA) signaling.
  • The precise role of p21-activated kinase 4 (PAK4) in this process is not fully understood.

Purpose of the Study:

  • To investigate the role of PAK4 in adipose tissue lipolysis and its potential as a therapeutic target for obesity.

Main Methods:

  • Studied PAK4's interaction with PKA and its effect on lipolysis in mouse models.
  • Utilized adipose tissue-specific overexpression and knockout of PAK4.
  • Administered PAK4 inhibitors to mice.
  • Analyzed phosphorylation of FABP4 and HSL.
  • Compared visceral fat from obese and lean individuals.

Main Results:

  • PKA targets PAK4 for degradation, influencing lipolysis.
  • PAK4 overexpression in mice reduced lipolysis and worsened obesity.
  • PAK4 knockout or inhibition enhanced lipolysis, reduced obesity and insulin resistance, and increased energy expenditure.
  • PAK4 directly phosphorylates FABP4 and HSL, hindering their interaction and inhibiting lipolysis.
  • Elevated PAK4 and specific phosphorylation sites were observed in visceral fat of obese individuals.

Conclusions:

  • PAK4 plays a critical role in regulating adipose tissue lipolysis through phosphorylation of FABP4 and HSL.
  • PAK4 inhibition represents a promising therapeutic strategy for managing obesity and related metabolic disorders.

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