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Published on: May 19, 2023
Modulation of adipose tissue phenotype and longevity-related gene expression by nuclear factor E2-related factor 2
Sai Zhang1,2, Bing Han1,2, Xue Wang1,2
1Department of Neurology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Purpose:
This study explores the role of nuclear factor E2-related factor 2 (Nrf2) in regulating adipose tissue phenotype and its potential mechanisms for promoting aging resistance in 3T3-L1 adipocytes. The study aims to evaluate the impact of Nrf2 knockdown on adipose phenotype transformation, focusing on brown adipose tissue (BAT) and white adipose tissue (WAT) marker genes, as well as longevity-related factors.
Methods:
3T3-L1 preadipocytes were differentiated into adipocytes using a standard MDI regimen. Nrf2 expression was knocked down via siRNA transfection. Gene expression was assessed using quantitative real-time PCR (qPCR), and protein levels were analyzed using Western blotting.
Results:
Nrf2 knockdown was confirmed by Western blot (p<0.001) and qPCR (p<0.001), showing a significant reduction in Nrf2 expression. Notably, this knockdown resulted in increased expression of BAT markers, including PGC-1α (p = 0.012), Dio2 (p = 0.020), and PRDM16 (p = 0.001), at both mRNA (PGC-1α [p = 0.012], Dio2 [p = 0.020], and PRDM16 [p = 0.001]) and protein (PGC-1α [p = 0.001]; Dio2 [p = 0.003]; PRDM16 [p = 0.007])levels. Conversely, WAT markers such as BMP4 (mRNA: p = 0.01; WB: p = 0.001), resistin (mRNA: p = 0.016; WB: p = 0.004), and Rb1 (mRNA: p = 0.03; WB: p = 0.003) were significantly downregulated. Additionally, levels of Cycs (mRNA: p = 0.024; WB: p = 0.037) and UCP1 (mRNA: p = 0.024; WB: p = 0.023) were elevated, indicating enhanced mitochondrial function and metabolic activity (P < 0.05). The knockdown also affected longevity-related proteins, Sirt1 (WB: p = 0.018) and AMPKα (WB: p = 0.021), underscoring Nrf2's role in metabolic regulation.
Conclusion:
Nrf2 knockdown in 3T3-L1 adipocytes promotes a transition towards a brown adipose phenotype and enhances the expression of longevity-related factors, suggesting Nrf2 as a potential therapeutic target for addressing aging-related metabolic decline.
