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Updated: Aug 20, 2025

Measuring the Rate of Lipolysis in Ex Vivo Murine Adipose Tissue and Primary Preadipocytes Differentiated In Vitro
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Rutaecarpin reduces lipids by DGKθ-dependent activation of PPARα

Di Wu1, Jiheng Wang1, Yongxing Chang1

  • 1Laboratory of Gene Therapy, Department of Biochemistry, College of Life Sciences, Shaanxi Normal University, Xi'an, China.

Obesity (Silver Spring, Md.)
|November 23, 2022
PubMed
Abstract

Insights

Rutaecarpin effectively reduces lipid accumulation by targeting diacylglycerol kinase theta (DGKθ). This natural compound offers a promising therapeutic strategy for managing lipid metabolic disorders.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Metabolomics

Background:

  • Lipid metabolic disorders represent a significant global health challenge with limited effective treatments.
  • Previous research identified diacylglycerol kinase theta (DGKθ) knockout in HepG2 cells as a cause of substantial lipid accumulation, highlighting DGKθ as a potential therapeutic target.
  • The development of novel therapeutic strategies for lipid disorders is urgently needed.

Purpose of the Study:

  • To investigate the potential of natural products in targeting lipid metabolism pathways.
  • To explore the mechanism of action of rutaecarpin in reducing lipid accumulation.
  • To validate DGKθ as a therapeutic target for lipid metabolic disorders.

Main Methods:

  • High-throughput screening of natural products using a DGKθ-T2A-luciferase knock-in HepG2 cell line.
  • RNA-sequencing and bioinformatic analysis to elucidate the molecular pathways affected by rutaecarpin.
  • In vitro and in vivo experiments, including Western blot and quantitative PCR, to confirm the effects of rutaecarpin on lipid metabolism in cell cultures and mouse models.

Main Results:

  • Rutaecarpin significantly enhances diacylglycerol kinase theta (DGKθ) expression.
  • Rutaecarpin demonstrably reduces lipid accumulation in oleic acid-induced HepG2 cells and high-fat diet-induced obese mice.
  • The lipid-lowering effect of rutaecarpin is mediated through the hepatocyte nuclear factor 1-beta (HNF1B)-DGKθ-peroxisome proliferator-activated receptor alpha (PPARα)-apolipoprotein C3 (APOC3) signaling pathway.

Conclusions:

  • Rutaecarpin is a potent natural compound effective in reducing lipid accumulation.
  • Targeting DGKθ presents a viable therapeutic strategy for managing lipid metabolic disorders.
  • A high-throughput screening platform utilizing reporter knock-in cell lines can accelerate the discovery of novel drugs for lipid metabolic disorders.

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