3-tert-Butyl-4-hydroxyanisole Impairs Hepatic Lipid Metabolism in Male Mice Fed with a High-Fat Diet.

Abstract

3-tert-Butyl-4-hydroxyanisole (3-BHA), one of the widely used food antioxidants, has been found to act as a potential obesogen by promoting adipogenesis in vitro and inducing white adipose tissue development in vivo. Whether 3-BHA-induced visceral obesity was accompanied by a disruption of hepatic lipid homeostasis in mammals remained unclear. In this study, we evaluated the effect of 3-BHA on the development of nonalcoholic fatty liver disease (NAFLD) in male C57BL/6J mice. After 18 weeks of oral administration of 10 mg/kg 3-BHA, the mice fed with a high-fat diet (HFD) had higher hepatic triglyceride concentrations (0.32 mg/mg protein) and severer steatosis (1.57 for the NAFLD score) than the control ones. The in vivo hepatic lipid deposition disturbed by 3-BHA was transcriptionally regulated by the genes involved in lipid uptake, de novo lipogenesis, fatty acid oxidation, and lipid export. The in vitro studies further confirmed that 24 h of exposure to 50 μM 3-BHA could induce intracellular oleic acid (OA) uptake and triglyceride accumulation (1.5-fold of the OA control) in HepG2 cells. Lipidomic analysis indicated the perturbation of 3-BHA in the levels of 30 lipid species related to sphingolipids, glycerophospholipids, and glycerolipids under HFD conditions. The findings herein first revealed the disruption effect of 3-BHA on hepatic lipid homeostasis, thus exacerbating the development of HFD-induced NAFLD.

• Authors: Zhendong Sun, Zhi Tang, Xiaoxi Yang, Qian S Liu, Jianqing Zhang, Qunfang Zhou, Guibin Jiang
• Journal: Environmental science & technology (Environ Sci Technol) Vol. 56 Issue 5 Pg. 3204-3213 (03 01 2022) ISSN: 1520-5851 [Electronic] United States
• PMID: 35133139 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Triglycerides
• Butylated Hydroxyanisole
• 3-tert-butyl-4-hydroxyanisole

Topics

• Animals
• Butylated Hydroxyanisole
• Diet, High-Fat
• Lipid Metabolism
• Liver (metabolism)
• Male
• Mammals
• Mice
• Mice, Inbred C57BL
• Non-alcoholic Fatty Liver Disease (chemically induced)
• Triglycerides (metabolism, pharmacology)