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Augmenting Nrf2 signaling pathway promotes adipocyte differentiation from human embryonic stem cells
Min Hee Park1, Da Yeon Gil1, Hyo-Won Han1
1Department of Chronic Diseases Convergence Research, Division of Intractable Diseases Research, Korea National Institute of Health, Republic of Korea; Korea National Stem Cell Bank, Chungcheongbuk-do, Republic of Korea.
Experimental Cell Research
|January 31, 2026
Summary
Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a key role in human adipocyte differentiation. Enhanced Nrf2 signaling promotes adipogenesis, increasing adipocyte size and lipid accumulation.
Area of Science:
- Cell Biology
- Molecular Biology
- Stem Cell Research
Background:
- Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor crucial for cellular defense mechanisms.
- The specific role of Nrf2 in human adipocyte differentiation is not well understood.
Purpose of the Study:
- To investigate the contribution of Nrf2 to human adipocyte differentiation.
- To explore the pro-adipogenic potential of enhanced Nrf2 signaling.
Main Methods:
- Utilized an in vivo teratoma model with human embryonic stem cells (hESCs) and KEAP1 gene deletion to enhance Nrf2 signaling.
- Performed quantitative transcriptomic analysis (TeratoScore) and Ingenuity Pathway Analysis.
- Conducted stepwise in vitro differentiation of hESCs into adipocytes.
Main Results:
- Enhanced Nrf2 signaling significantly increased adipocyte size and area within teratomas.
- Transcriptomic analysis revealed activation of adipogenesis-related signaling networks, with increased expression of key adipogenic markers (FABP4, PPARG, ADIPOQ, CEBPA).
- In vitro differentiation showed increased lipid-droplet accumulation, supporting a pro-adipogenic role for Nrf2. PAX3 was identified as a potential transcriptional target.
Conclusions:
- Nrf2 plays a significant pro-adipogenic role in human adipogenesis.
- Enhanced Nrf2 signaling promotes adipocyte differentiation and lipid accumulation.
- Nrf2 signaling may be a novel target for regulating adipogenesis.
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