Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan, 430071, Huibei, China.
Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan, 430071, Huibei, China.
Food Chem Toxicol. 2018 Oct;120:24-31. doi: 10.1016/j.fct.2018.06.056. Epub 2018 Jun 26.
Caffeine is contained within many drinks and food that are consumed daily. Prenatal caffeine ingestion (PCI) is a risk factor for intrauterine growth retardation (IUGR). We previously observed that PCI inhibits scavenger receptor class B type I (SR-BI)-mediated cholesterol uptake in fetal adrenals, subsequently decreasing glucocorticoid synthesis and inducing IUGR. In the present study, we aimed to investigate the long-term effects of PCI on adrenal glucocorticoid synthesis in adult male offspring rats. After establishing the PCI-induced IUGR, adult male offspring was injected intraperitoneally with 5 mg/kg·d lipopolysaccharide (LPS) for 2 days to induce acute stress. We observed persistent inhibition of SR-BI expression in PCI adrenals before and after stress. Compared with the controls, the PCI offspring had higher corticosterone concentrations after stress. The serum cholesterol concentration was stable without intergroup differences before and after stress. The cholesterol concentration in PCI adrenals showed a higher decrease rate than that of the control after stress. In summary, PCI induced long-term alterations in SR-BI expression and glucocorticoid synthesis in adult male offspring rat adrenals. Cholesterol has to be over-consumed in PCI adrenals against acute stress. This study provides an experimental basis to explain the susceptibility of IUGR offspring to metabolic diseases in adults.
咖啡因存在于许多日常饮用和食用的饮料及食物中。产前咖啡因摄入(PCI)是宫内生长迟缓(IUGR)的一个风险因素。我们之前观察到 PCI 抑制了胎儿肾上腺中的清道夫受体 B 类 I 型(SR-BI)介导的胆固醇摄取,随后减少了糖皮质激素的合成并导致 IUGR。在本研究中,我们旨在研究 PCI 对成年雄性子代大鼠肾上腺糖皮质激素合成的长期影响。在建立 PCI 诱导的 IUGR 后,成年雄性子代大鼠腹膜内注射 5mg/kg·d 脂多糖(LPS)连续 2 天以诱导急性应激。我们观察到应激前后 PCI 肾上腺中的 SR-BI 表达持续受到抑制。与对照组相比,应激后 PCI 子代的皮质酮浓度更高。应激前后血清胆固醇浓度在各组间均无差异且保持稳定。应激后 PCI 肾上腺中的胆固醇浓度下降速度高于对照组。总之,PCI 导致成年雄性子代大鼠肾上腺中的 SR-BI 表达和糖皮质激素合成发生长期改变。在急性应激下,PCI 肾上腺中必须过度消耗胆固醇。本研究为解释 IUGR 子代在成年期易患代谢疾病的机制提供了实验依据。