Related Experiment Video

Updated: May 8, 2026

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

PKCβ II antagonizes O-GlcNAcylated FOXO4 and inhibits lipid synthesis

Hua Fu1, Yuqin Li2, Pengzhou Li2

  • 1Department of Pathology, Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan Province, People's Republic of China.

Apoptosis : an International Journal on Programmed Cell Death
|May 7, 2026
PubMed
Abstract

Insights

Obesity and metabolic disorders are global health issues. This study reveals how FOXO4 regulation impacts lipid synthesis, offering potential therapeutic targets.

Area of Science:

  • Metabolic Regulation
  • Molecular Biology
  • Obesity Research

Background:

  • Obesity and metabolic disorders present significant global health challenges.
  • Targeting lipid synthesis is a promising therapeutic strategy, but mechanisms are not fully understood.

Purpose of the Study:

  • To elucidate the regulatory mechanisms of lipid synthesis.
  • To investigate the role of FOXO4 in lipid metabolism and its regulation.

Main Methods:

  • Gene expression analysis (RT-qPCR, Western blot).
  • Lipid droplet quantification (Nile Red staining).
  • Biochemical assays (ELISA) for lipid levels.
  • Molecular interaction studies (ChIP, Dual-luciferase, Co-IP).
  • Subcellular localization analysis (fractionation, immunofluorescence).

Main Results:

  • FOXO4 downregulation after bariatric surgery reduced lipogenic enzyme transcription (ACACA, HMGCR).
  • O-GlcNAcylation and phosphorylation at specific sites (S261, T451) modulated FOXO4 nuclear translocation and lipogenic gene expression.
  • FOXO4 deletion suppressed lipid synthesis under high-fat diet (HFD) conditions.

Conclusions:

  • Elevated O-GlcNAc transferase (OGA) inhibited FOXO4 nuclear translocation, decreasing lipogenic gene expression and lipid synthesis.
  • PKCβII-mediated phosphorylation also influenced FOXO4 stability and function.
  • These findings reveal a novel regulatory pathway for lipid synthesis involving FOXO4.
Keywords:
ACACAFOXO4HMGCRLipid synthesisO-GlcNAcylationPKCβIIPhosphorylation

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