Gestational bisphenol A exposure impairs hepatic lipid metabolism by altering mTOR/CRTC2/SREBP1 in male rat offspring. (20th September 2022)

• Record Type: Journal Article
• Authors: Yang, Q; Mao, Y; Wang, J; Yu, H; Zhang, X; Pei, X; Duan, Z; Xiao, C; Ma, M
• Is Part Of: Human & experimental toxicology. Volume 41(2022)
• Publication Date: 2022-09-20
• Subjects: Gestational BPA exposure -- male offspring -- lipid metabolism -- mTOR -- CRTC2 -- SREBP-1; Toxicology -- Periodicals; 615.9
• DOI: 10.1177/09603271221129852
• Languages: English
• ISSNs: 0960-3271

Abstract

Lipid metabolism is an important biochemical process in the body. Recent studies have found that environmental endocrine disruptors play an important role in the regulation of lipid metabolism. Bisphenol A (BPA), a common environmental endocrine disruptor, has adverse effects on lipid metabolism, but the mechanism is still unclear. This study aimed to investigate the effects of gestational BPA exposure on hepatic lipid metabolism and its possible mechanism in male offspring. The pregnant Sprague-Dawley rats were exposed to BPA (0, 0.05, 0.5, 5 mg/kg/day) from day 5 to day 19 of gestation to investigate the levels of triglyceride (TG) and total cholesterol (TC), and the expression of liver lipid metabolism-related genes in male offspring rats. The results showed that compared with the control group, the TG and TC levels in serum and liver in BPA-exposed groups was increased. And the expressions of liver fatty acid oxidation related genes, such as peroxisome proliferators-activated receptor α (PPARα) and carnitine palmitoyl transferase 1α (CPT1α), were down-regulated. However, the expressions of fatty acid synthesis related genes, such as sterol regulatory element binding proteins 1 (SREBP-1), acetyl-CoA carboxylase 1 (ACC1), fatty acid synthase (FAS) and stearoyl-CoA desaturase 1 (SCD-1), were up-regulated. The increased protein levels of mTOR and p-CRTC2 suggested that CREB-regulated transcription coactivator 2 (CRTC2) might be an important mediator in the mTOR/SREBP-1 pathway. In conclusion, these results demonstrated that mTOR/CRTC2/SREBP-1 could be affected by gestational BPA exposure, which may involve in the lipid metabolic disorders in later life.