Transcriptomic Profiling Identifies Hub Transcription Factors Associated with the Protective Effects of Licochalcone A Against HFD-Induced MASLD
- 1School of Medical Technology and Engineering, Henan University of Science and Technology, 263 Kaiyuan Ave, Luoyang 471023, China
- 2College of Animal Science and Technology, Henan University of Science and Technology, 263 Kaiyuan Ave, Luoyang 471023, China
Abstract
Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD) lacks approved specific pharmacological treatments and exhibits complex pathogenesis. Licochalcone A (LA), a flavonoid extracted from Glycyrrhiza glabra, possesses anti-inflammatory and lipid-modulating activities, yet its protective effects and transcriptional regulatory mechanisms against MASLD remain poorly defined. Methods: We established an HFD-induced MASLD mouse model to assess the in-vivo protective effect of LA. Hepatic RNA-sequencing was performed to profile transcription factor (TF) expression and identify differentially expressed transcription factors (DE-TFs). Functional enrichment and protein–protein interaction (PPI) network analysis were conducted to characterize DE-TFs and screen hub TFs. RT-qPCR was used to validate the expression patterns of identified hub TFs. Results: LA administration attenuated hepatic lipid deposition in HFD-fed MASLD mice. In total, 149 DE-TFs were identified, including 95 DE-TFs from the comparison of HFD versus control mice and 122 DE-TFs from LA-treated mice versus HFD mice, with 68 DE-TFs shared between the two comparisons. Functional enrichment indicated that these DE-TFs were associated with RNA polymerase II-dependent transcription, nuclear components, DNA binding, signal transduction, and metabolic-disease-related pathways. Nine hub TFs (Myc, Fos, Runx1, Mef2c, Spi1, Sox9, E2f1, Cebpa, and Pparg) were screened via PPI analysis. Seven hub TFs were up-regulated, while Cebpa and Pparg were down-regulated in MASLD mice; LA intervention partly reversed this dysregulated expression profile, as further verified by RT-qPCR. Conclusions: LA mitigates the development of HFD-provoked MASLD-associated hepatic lesions and is associated with partially restored transcript levels of aberrantly expressed hub TFs in mice. This work provides transcriptome-level resources for understanding LA-mediated hepatoprotection against HFD-induced MASLD development and highlights candidate TF targets relevant to MASLD research.
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BibTeX
@article{zhao2026transcriptomic,
title = {{Transcriptomic Profiling Identifies Hub Transcription Factors Associated with the Protective Effects of Licochalcone A Against HFD-Induced MASLD}},
author = {Shanshan Zhao and Bohan Lei and Rongxia Li and Shuai Wang},
journal = {Nutrients},
year = {2026},
month = oct,
doi = {10.3390/nu18213564},
url = {https://www.mdpi.com/2072-6643/18/21/3564},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Transcriptomic Profiling Identifies Hub Transcription Factors Associated with the Protective Effects of Licochalcone A Against HFD-Induced MASLD
AU - Shanshan Zhao
AU - Bohan Lei
AU - Rongxia Li
AU - Shuai Wang
PY - 2026
DA - 2026/10/28
JO - Nutrients
DO - 10.3390/nu18213564
UR - https://www.mdpi.com/2072-6643/18/21/3564
AB - Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD) lacks approved specific pharmacological treatments and exhibits complex pathogenesis. Licochalcone A (LA), a flavonoid extracted from Glycyrrhiza glabra, possesses anti-inflammatory and lipid-modulating activities, yet its protective effects and transcriptional regulatory mechanisms against MASLD remain poorly defined. Methods: We established an HFD-induced MASLD mouse model to assess the in-vivo protective effect of LA. Hepatic RNA-sequencing was performed to profile transcription factor (TF) expression and identify differentially expressed transcription factors (DE-TFs). Functional enrichment and protein–protein interaction (PPI) network analysis were conducted to characterize DE-TFs and screen hub TFs. RT-qPCR was used to validate the expression patterns of identified hub TFs. Results: LA administration attenuated hepatic lipid deposition in HFD-fed MASLD mice. In total, 149 DE-TFs were identified, including 95 DE-TFs from the comparison of HFD versus control mice and 122 DE-TFs from LA-treated mice versus HFD mice, with 68 DE-TFs shared between the two comparisons. Functional enrichment indicated that these DE-TFs were associated with RNA polymerase II-dependent transcription, nuclear components, DNA binding, signal transduction, and metabolic-disease-related pathways. Nine hub TFs (Myc, Fos, Runx1, Mef2c, Spi1, Sox9, E2f1, Cebpa, and Pparg) were screened via PPI analysis. Seven hub TFs were up-regulated, while Cebpa and Pparg were down-regulated in MASLD mice; LA intervention partly reversed this dysregulated expression profile, as further verified by RT-qPCR. Conclusions: LA mitigates the development of HFD-provoked MASLD-associated hepatic lesions and is associated with partially restored transcript levels of aberrantly expressed hub TFs in mice. This work provides transcriptome-level resources for understanding LA-mediated hepatoprotection against HFD-induced MASLD development and highlights candidate TF targets relevant to MASLD research.
SN - 2072-6643
ER -