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.

Liver Lipidomics Analysis Revealed the Novel Ameliorative Mechanisms of L-Carnitine on High-Fat Diet-Induced NAFLD Mice

“…The correlation analysis showed that they were negatively correlated with NAFLD. Similar observations were reported by Sun et al that some SM species, such as SM(d18:1/16:0), were dramatically reduced in NAFLD mice [ 59 ]. L-carnitine supplementation significantly increased the hepatic levels of the three sphingolipids.…”

“…Cer is involved in various bioactivities, such as cell differentiation, apoptosis and autophagy, while SM regulates cell proliferation and survival [ 58 ]. The dysregulation of sphingolipid metabolism drove the progression of NAFLD [ 59 ]. In this study, both total Cer and SM were reduced in the liver of the NAFLD mice.…”

Chewing the fat: How lipidomics is changing our understanding of human health and disease in 2022

“…Bibliometric analyses of clinical lipidomics publications in 2022 using Scopus search terms “lipidomics” AND “clinic*” on 15 th December 2022 …”

“…Bibliometric analyses of clinical lipidomics publications in 2022 according to separation techniques, detectors, and RPLC columns used …”

“…,51,[279][280][281][282][283][284][285][286][287][288][289][290][291][292][293] MetS277,294,295 and obesity 277,[295][296][297][298][299][300][301][302][303][304][305]. Coleman et al investigated the pathogenesis and involvement of the gastrointestinal tract with the syndrome through multiple experiments including an untargeted RPLC-MS/MS analysis of faecal samples of people with MetS and healthy controls.…”