Modulation of adipose tissue phenotype and longevity-related gene expression by nuclear factor E2-related factor 2 knockdown in 3T3-L1 cells.

IF 2.4 4区医学 Q3 ENDOCRINOLOGY & METABOLISM

Hormones-International Journal of Endocrinology and Metabolism Pub Date : 2025-05-09 DOI:10.1007/s42000-025-00669-9

Sai Zhang, Bing Han, Xue Wang, Xiaoyang Yuan

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引用次数: 0

Abstract

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.

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3T3-L1细胞中核因子e2相关因子2敲低对脂肪组织表型和长寿相关基因表达的调节

目的：探讨核因子e2相关因子2 （Nrf2）在调节脂肪组织表型中的作用及其促进3T3-L1脂肪细胞抗衰老的潜在机制。本研究旨在评估Nrf2敲低对脂肪表型转化的影响，重点关注棕色脂肪组织（BAT）和白色脂肪组织（WAT）标记基因，以及长寿相关因素。方法：采用标准MDI方案将3T3-L1前脂肪细胞分化为脂肪细胞。通过siRNA转染降低Nrf2的表达。采用实时荧光定量PCR （qPCR）检测基因表达，Western blotting检测蛋白水平。结论：Nrf2在3T3-L1脂肪细胞中下调可促进脂肪向棕色表型转变，并增强长寿相关因子的表达，提示Nrf2可能是解决衰老相关代谢下降的潜在治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Hormones-International Journal of Endocrinology and Metabolism ENDOCRINOLOGY & METABOLISM-

CiteScore

5.90

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Hormones-International Journal of Endocrinology and Metabolism is an international journal published quarterly with an international editorial board aiming at providing a forum covering all fields of endocrinology and metabolic disorders such as disruption of glucose homeostasis (diabetes mellitus), impaired homeostasis of plasma lipids (dyslipidemia), the disorder of bone metabolism (osteoporosis), disturbances of endocrine function and reproductive capacity of women and men. Hormones-International Journal of Endocrinology and Metabolism particularly encourages clinical, translational and basic science submissions in the areas of endocrine cancers, nutrition, obesity and metabolic disorders, quality of life of endocrine diseases, epidemiology of endocrine and metabolic disorders.