School of Public Health, China Medical University, Shenyang, 110122, China.
Metabolic Signaling and Disease Program, Sanford-Burnham Medical Research Institute, Orlando, FL, 32827, USA.
Biochem Biophys Res Commun. 2018 Sep 3;503(1):264-270. doi: 10.1016/j.bbrc.2018.06.013. Epub 2018 Jun 25.
The maintenance of healthy adipose tissues is essential for efficient regulation of energy homeostasis. Nuclear factor-erythroid 2-related factor 1 (NFE2L1, also known as Nrf1), a CNC-bZIP protein, is a master regulator of the cellular adaptive response to stresses. To investigate the role of NFE2L1 in adipocytes, we bred a line of mice with adipocyte-specific Nfe2l1 knockout (Nfe2l1(f)-KO), and found that Nfe2l1(f)-KO mice exhibited a dramatically reduced subcutaneous adipose tissue (SAT) mass, insulin resistance, adipocyte hypertrophy, and severe adipose inflammation. Mechanistic studies revealed that Nfe2l1 deficiency may disturb the expression of lipolytic genes in adipocytes, leading to adipocyte hypertrophy followed by inflammation, pyroptosis, and insulin resistance. Our findings reveal a novel role for NFE2L1 in regulating adipose tissue plasticity and energy homeostasis.
健康脂肪组织的维持对于有效调节能量平衡至关重要。核因子-红细胞 2 相关因子 1（NFE2L1，也称为 Nrf1）是 CNC-bZIP 蛋白家族的一员，是细胞对压力产生适应性反应的主要调节因子。为了研究 NFE2L1 在脂肪细胞中的作用，我们培育了一种脂肪细胞特异性 Nfe2l1 敲除（Nfe2l1(f)-KO）的小鼠，发现 Nfe2l1(f)-KO 小鼠的皮下脂肪组织（SAT）质量显著减少，表现出胰岛素抵抗、脂肪细胞肥大和严重的脂肪炎症。机制研究表明，Nfe2l1 缺失可能会干扰脂肪细胞中脂肪分解基因的表达，导致脂肪细胞肥大，随后发生炎症、细胞焦亡和胰岛素抵抗。我们的研究结果揭示了 NFE2L1 在调节脂肪组织可塑性和能量平衡方面的新作用。
