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Updated: Jan 17, 2026

Author Spotlight: Semi-Automated Isolation of the Stromal Vascular Fraction from Murine White Adipose Tissue Using a Tissue Dissociator
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Author Spotlight: Semi-Automated Isolation of the Stromal Vascular Fraction from Murine White Adipose Tissue Using a Tissue Dissociator

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NRF2-REGγ-ACADM/KLF15 Signaling Pathway Regulates the Browning of White Adipose Tissue to Modulate Obesity

Hui Chen1,2, Qiujing Guan3, Shuangming Gong3

  • 1Department of Trauma-Emergency & Critical Care Medicine, Shanghai Fifth People's Hospital, Fudan University, Shanghai, 200240, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|September 19, 2025
PubMed

Insights

REGγ protein is upregulated in obesity. Inhibiting REGγ reduces fat accumulation and insulin resistance, offering a potential new treatment target for obesity and related metabolic diseases.

Area of Science:

  • Metabolic disease research
  • Adipose tissue biology
  • Obesity research

Background:

  • Obesity is a major risk factor for diabetes, cardiovascular diseases, and cancers.
  • Browning of white adipose tissue (WAT) is a key strategy for obesity and metabolic disease treatment.
  • Understanding molecular mechanisms of fat thermogenesis is crucial for developing interventions.

Purpose of the Study:

  • To investigate the role of REGγ in obesity and related metabolic dysfunction.
  • To elucidate the molecular mechanisms by which REGγ regulates adipose tissue function.
  • To evaluate REGγ as a potential therapeutic target for obesity.

Main Methods:

  • Analysis of REGγ expression in adipose tissue from obese individuals and mice.
  • Investigating the effects of REGγ deficiency on fat deposition, energy expenditure, and insulin resistance in mice.
  • Examining the molecular pathways regulated by REGγ, including ACADM, KLF15, and UCP1 signaling.
  • Assessing the impact of REGγ inhibition on high-fat diet-induced obesity.

Main Results:

  • REGγ expression is significantly upregulated in the adipose tissue of obese individuals and mice.
  • REGγ deficiency reduces fat deposition, enhances adipose tissue energy expenditure, and protects against high-fat diet-induced obesity and insulin resistance.
  • REGγ regulates WAT browning by modulating ACADM and KLF15-UCP1 signaling.
  • Inhibition of REGγ in inguinal WAT alleviates high-fat diet-induced obesity.

Conclusions:

  • REGγ plays a critical role in promoting obesity and insulin resistance.
  • Targeting REGγ, particularly through its inhibition in adipose tissue, presents a promising therapeutic strategy for obesity.
  • The NRF2-REGγ axis is implicated in facilitating adipose tissue dysfunction and obesity development.
Keywords:
PSME3browning of white adipose tissueobesityubiquitin‐independent protein degradation

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