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Deficiency in Nrf2 transcription factor decreases adipose tissue mass and hepatic lipid accumulation in

Jialin Xu1, Ajay C Donepudi, Vijay R More

  • 1Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island, USA; Institute of Biochemistry and Molecular Biology, College of Life and Health Sciences, Northeastern University, Shenyang, People's Republic of China.

Obesity (Silver Spring, Md.)
|December 3, 2014
PubMed
Abstract

Insights

Nrf2 deficiency in obese mice reduced fat and liver lipids but worsened insulin resistance and dyslipidemia. This highlights Nrf2

Area of Science:

  • Metabolic research
  • Molecular biology
  • Obesity and diabetes research

Background:

  • Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor regulating antioxidant and detoxification genes.
  • Its role in metabolic dysregulation, particularly in obesity and type 2 diabetes, remains complex and requires further elucidation.

Purpose of the Study:

  • To investigate the impact of Nrf2 deficiency on insulin resistance and lipid accumulation in the liver and white adipose tissue of obese mice.

Main Methods:

  • Generation of obese Nrf2-deficient (OB-Nrf2KO) mice using the Lep(ob/ob) model.
  • Assessment of obesity and type 2 diabetes pathogenesis in wild-type, Nrf2-deficient, obese, and obese Nrf2-deficient mice.
  • Determination of hepatic lipid content, clearance, and very low-density lipoprotein (VLDL) secretion in OB and OB-Nrf2KO mice.

Main Results:

  • OB-Nrf2KO mice showed reduced white adipose tissue mass and suppressed adipogenic/lipogenic gene expression compared to obese mice.
  • Nrf2 deficiency exacerbated hyperglycemia and reduced insulin-stimulated Akt phosphorylation.
  • In obese mice, Nrf2 deficiency decreased hepatic lipid accumulation but enhanced VLDL secretion, leading to dyslipidemia (increased triglycerides, decreased HDL-cholesterol).

Conclusions:

  • Nrf2 deficiency in obese mice reduced adipose tissue and hepatic lipid accumulation but induced insulin resistance and dyslipidemia.
  • Nrf2 plays a dual role in metabolic dysregulation, promoting lipid accumulation in lean conditions but mitigating it in obesity while potentially impairing glucose homeostasis.

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