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Tamarixetin Improves Metabolic Dysfunction by Inhibiting the p300-Mediated Epigenetic Activation of Pyruvate

Ji-Hye Song1, Jangho Lee1, Hyo-Jin Kim2

  • 1Food Functionality Research Division, Korea Food Research Institute, Wanju-gun, Republic of Korea.

Journal of Medicinal Food
|June 30, 2026
PubMed

Insights

Tamarixetin (Tx) combats obesity by epigenetically suppressing lipogenic genes like Pdk4. This natural flavonoid restores metabolic signaling and enhances insulin sensitivity, offering a promising therapeutic for metabolic disorders.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Epigenetics

Background:

  • Metabolic disorders like obesity and insulin resistance are characterized by excessive lipid accumulation.
  • Current therapeutic strategies for these conditions are limited.
  • Tamarixetin (Tx), a natural flavonoid, has potential pharmacological benefits but its role in lipid metabolism is not well understood.

Purpose of the Study:

  • To investigate the metabolic benefits of Tamarixetin (Tx).
  • To elucidate the molecular mechanisms underlying Tx's effects on lipid metabolism.
  • To evaluate Tx in a Western diet-induced obesity model.

Main Methods:

  • Transcriptomic profiling to analyze gene expression changes.
  • Molecular docking to predict Tx interaction with p300 histone acetyltransferase.
  • Epigenetic analysis of H3K9 acetylation at the Pdk4 promoter.
  • In vitro studies to assess insulin sensitivity and signaling pathways.

Main Results:

  • Tx reversed Western diet-induced gene expression patterns, suppressing Pdk4 and inducing Phlda1.
  • Tx interacts with the p300 HAT domain, reducing H3K9 acetylation at the Pdk4 promoter.
  • Epigenetic inhibition of Pdk4 activated p38/AMPK signaling, upregulating PPARGC1A and CPT1A, and improving insulin sensitivity.

Conclusions:

  • Tamarixetin (Tx) acts as a novel epigenetic modulator.
  • Tx simultaneously suppresses lipogenic gene expression and restores metabolic signaling pathways.
  • Tx is a promising natural compound for therapeutic intervention in metabolic disorders.
Keywords:
AMPK signalingPDK4epigenetic regulationmetabolic dysfunctiontamarixetin

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