Reproductive Center of Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fujian Provincial Reproductive Medical Center, Fuzhou 350001, China.
Reproductive Center of Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fujian Provincial Reproductive Medical Center, Fuzhou 350001, China; Fujian Medical University, Fuzhou 350001, China.
Toxicology. 2022 May 15;473:153194. doi: 10.1016/j.tox.2022.153194. Epub 2022 Apr 30.
Accumulating evidence suggests the role of developmental exposure of bisphenol A (BPA) in metabolic disorders. However, the underlying mechanism remains unclear. Using a rat model, we investigated the neonatal exposure of BPA on lipid metabolism in adult and the underlying mechanisms. From postnatal day1(PND1) to PND10, male rats were exposed to BPA via daily subcutaneous injection with 10 µg/100 µL BPA (1.24-0.5 mg/kg body weight/day, a dose below the US-EPA LOAEL). After fasting for 8 h, adult rats aged 80 days showed elevated levels of serum free fatty acid (FFA), glycerol and glucose, and increased levels of FFA and glycerol in visceral adipose tissue. The expression levels of key enzymes of lipolysis, adipose triglyceride lipase (Atgl) and hormone-sensitive lipase (Hsl), were increased in visceral adipose tissue from BPA-exposed rats after fasting. On the other hand, transcription levels of lipogenic genes remained unchanged. Differentiation of visceral adipocyte in rats takes place neonatally. In our study, neonatal BPA exposure induced DNA hypomethylation of Atgl in visceral adipose tissue. In 3T3-L1 cell, administration of 10 mol/L BPA throughout the differentiation stage led to DNA hypomethylation and increased expression of Atgl. Our results suggest that neonatal exposure of BPA led to increased lipolysis of visceral adipose tissue in young adults, which will predispose individuals to multiple metabolic disorders. The DNA hypomethylation of Atgl might be one of the mechanisms underneath the long-lasting effect of neonatal BPA exposure.
越来越多的证据表明，双酚 A（BPA）在发育过程中的暴露会导致代谢紊乱。然而，其潜在机制尚不清楚。本研究使用大鼠模型，探讨了 BPA 对新生大鼠成年后脂质代谢的影响及其潜在机制。从出生后第 1 天（PND1）到第 10 天（PND10），雄性大鼠每天通过皮下注射 10μg/100μL BPA（1.24-0.5mg/kg 体重/天，这一剂量低于美国环保署的 LOAEL）进行暴露。禁食 8 小时后，80 天大的成年大鼠表现出血清游离脂肪酸（FFA）、甘油和葡萄糖水平升高，以及内脏脂肪组织中 FFA 和甘油水平升高。禁食后，BPA 暴露大鼠的内脏脂肪组织中脂肪分解关键酶——脂肪甘油三酯脂肪酶（Atgl）和激素敏感性脂肪酶（Hsl）的表达水平升高。另一方面，脂肪生成基因的转录水平保持不变。大鼠内脏脂肪细胞的分化发生在新生期。在本研究中，新生期 BPA 暴露导致内脏脂肪组织中 Atgl 的 DNA 低甲基化。在 3T3-L1 细胞中，整个分化阶段给予 10μmol/L 的 BPA 导致 Atgl 的 DNA 低甲基化和表达增加。我们的研究结果表明，新生期 BPA 暴露导致年轻成年大鼠内脏脂肪组织脂肪分解增加，这将使个体易患多种代谢紊乱。Atgl 的 DNA 低甲基化可能是新生期 BPA 暴露长期影响的机制之一。
