The widespread usage of 3-tert-butyl-4-hydroxyanisole (3-BHA) as an anthropogenic antioxidant has caused considerable environmental contamination and frequent detection in diverse human-derived samples. 3-BHA can promote adipogenesis and impair hepatic lipid metabolism, while its effects on renal lipid homeostasis remain to be uncertain. Herein, using the human kidney 2 (HK-2) cell experiments, 3-BHA was found to cause a significant reduction in lipid accumulation of the HK-2 cells in both exposure concentration- and duration-dependent manners. Exposure to 3-BHA lowered the transcriptional expressions of sterol regulatory element-binding protein 1 (SREBP1) and acetyl-CoA carboxylase (ACC), as well as ACC activity, indicating the inhibition in the process of de novo lipogenesis in HK-2 cells. On this basis, the mechanism study suggested that the reduced glucose absorption and accelerated glycolysis were concomitantly involved. The antagonism of 3-BHA on the transactivation of androgen receptor (AR) contributed to the lowered de novo lipogenesis and the consequent intracellular lipid reduction. The metabolomics data further confirmed the imbalance of lipid homeostasis and dysregulation of de novo lipogenesis. The new findings on the impaired renal lipid metabolism induced by 3-BHA warranted proper care about the usage of this chemical as a food additive.

3-叔丁基-4-羟基茴香醚 (3-BHA) 作为人为抗氧化剂的广泛使用已造成相当大的环境污染，并在各种人源样品中频繁检测到。3-BHA可促进脂肪生成并损害肝脏脂质代谢，而其对肾脏脂质稳态的影响尚不明确。在此，使用人肾 2 (HK-2) 细胞实验，发现 3-BHA 以暴露浓度和持续时间依赖性方式显着减少 HK-2 细胞的脂质积累。暴露于 3-BHA 降低了甾醇调节元件结合蛋白 1 ( SREBP1 ) 和乙酰辅酶 A 羧化酶 ( ACC ) 的转录表达，以及 ACC 活性，表明抑制过程HK-2 细胞中的从头脂肪生成。在此基础上，机制研究表明，葡萄糖吸收减少和糖酵解加速是同时参与的。3-BHA 对雄激素受体 (AR) 反式激活的拮抗作用有助于降低从头脂肪生成和随之而来的细胞内脂质减少。代谢组学数据进一步证实了脂质体内平衡的失衡和新生脂肪生成的失调。关于 3-BHA 引起的肾脂质代谢受损的新发现保证了对该化学品作为食品添加剂的使用给予适当的关注。