3-tert-Butyl-4-hydroxyanisole perturbs renal lipid metabolism in vitro by targeting androgen receptor-regulated de novo lipogenesis

• Published in: Ecotoxicology and environmental safety Vol. 258; p. 114979
• Main Authors: Wang, Xiaoyun, Sun, Zhendong, Gao, Yurou, Liu, Qian S., Yang, Xiaoxi, Liang, Jiefeng, Ren, Jing, Ren, Zhihua, Zhou, Qunfang, Jiang, Guibin
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 15.06.2023; Elsevier
• Subjects: 3-tert-Butyl-4-hydroxyanisole; Androgen receptor; De novo lipogenesis; Human kidney 2 cells; Humans; Lipid Metabolism; Lipids; Lipogenesis; Receptors, Androgen - genetics; Renal lipid homeostasis; 3-tert-Butyl-4-hydroxyanisole; Renal lipid homeostasis; Human kidney 2 cells; De novo lipogenesis; Androgen receptor
• ISSN: 0147-6513; 1090-2414
• DOI: 10.1016/j.ecoenv.2023.114979

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. [Display omitted] •3-tert-Butyl-4-hydroxyanisole (3-BHA) reduced lipid deposition in the human kidney 2 (HK-2) cells.•3-BHA lowered de novo synthesis by antagonizing the transactivation of androgen receptor.•Reduced glucose absorption and accelerated glycolysis occurred in 3-BHA- treated HK-2 cells.•3-BHA-caused impairment in renal lipid homeostasis was confirmed by the metabolomics data.