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低剂量发育性双酚 A 暴露改变 Fischer 344 大鼠后代的脂肪酸代谢。

Low-dose developmental bisphenol A exposure alters fatty acid metabolism in Fischer 344 rat offspring.

机构信息

Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Sweden.

Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Sweden.

出版信息

Environ Res. 2018 Oct;166:117-129. doi: 10.1016/j.envres.2018.05.023. Epub 2018 Jun 7.

Abstract

BACKGROUND

Bisphenol A (BPA) is an endocrine disruptor and also a suggested obesogen and metabolism-disrupting chemical. Accumulating data indicates that the fatty acid (FA) profile and their ratios in plasma and other metabolic tissues are associated with metabolic disorders. Stearoyl-CoA desaturase 1 (SCD-1) is a key regulator of lipid metabolism and its activity can be estimated by dividing the FA product by its precursor measured in blood or other tissues.

OBJECTIVE

The primary aim of this study was to investigate the effect of low-dose developmental BPA exposure on tissue-specific FA composition including estimated SCD-1 activity, studied in 5- and 52-week (wk)-old Fischer 344 (F344) rat offspring.

METHODS

Pregnant F344 rats were exposed to BPA via their drinking water corresponding to 0: [CTRL], 0.5: [BPA0.5], or 50 µg/kg BW/day: [BPA50], from gestational day 3.5 until postnatal day 22.

RESULTS

BPA0.5 increased SCD-16 (estimated as the 16:1n-7/16:0 ratio) and SCD-18 (estimated as the 18:1n-9/18:0 ratio) indices in inguinal white adipose tissue triglycerides (iWAT-TG) and in plasma cholesterol esters (PL-CE), respectively, in 5-wk-old male offspring. In addition, BPA0.5 altered the FA composition in male offspring, e.g. by decreasing levels of the essential polyunsaturated FA linoleic acid (18:2n-6) in iWAT-and liver-TG. No differences were observed regarding the studied FAs in 52-wk-old offspring, although a slightly increased BW was observed in 52-wk-old female offspring.

CONCLUSIONS

Low-dose developmental BPA exposure increased SCD-16 in iWAT-TG and SCD-18 in PL-CE of male offspring, which may reflect higher SCD-1 activity in these tissues. Altered desaturation activity and signs of altered FA composition are novel findings that may indicate insulin resistance in the rat offspring. These aforementioned results, together with the observed increased BW, adds to previously published data demonstrating that BPA can act as a metabolism disrupting chemical.

摘要

背景

双酚 A(BPA)是一种内分泌干扰物,也是一种被认为会导致肥胖和代谢紊乱的化学物质。越来越多的证据表明,血浆和其他代谢组织中的脂肪酸(FA)谱及其比值与代谢紊乱有关。硬脂酰辅酶 A 去饱和酶 1(SCD-1)是脂质代谢的关键调节因子,其活性可以通过将血液或其他组织中测量的 FA 产物与其前体相除来估计。

目的

本研究的主要目的是研究低剂量发育性 BPA 暴露对组织特异性 FA 组成的影响,包括估计的 SCD-1 活性,在 5 周和 52 周(wk)龄的 Fischer 344(F344)大鼠后代中进行研究。

方法

妊娠 F344 大鼠从妊娠第 3.5 天到产后第 22 天通过饮用水暴露于 BPA,浓度分别为 0: [CTRL]、0.5: [BPA0.5]或 50μg/kg BW/天:[BPA50]。

结果

BPA0.5 增加了腹股沟白色脂肪组织甘油三酯(iWAT-TG)中 SCD-16(估计为 16:1n-7/16:0 比值)和 SCD-18(估计为 18:1n-9/18:0 比值)指数,以及雄性后代血浆胆固醇酯(PL-CE)中的 SCD-18 指数。此外,BPA0.5 改变了雄性后代的 FA 组成,例如通过降低腹股沟脂肪组织和肝脏 TG 中的必需多不饱和脂肪酸亚油酸(18:2n-6)的水平。在 52 周龄的后代中没有观察到研究中的 FA 存在差异,尽管观察到 52 周龄雌性后代的 BW 略有增加。

结论

低剂量发育性 BPA 暴露增加了雄性后代 iWAT-TG 中的 SCD-16 和 PL-CE 中的 SCD-18,这可能反映了这些组织中 SCD-1 活性的增加。改变的去饱和活性和 FA 组成的迹象是新的发现,这可能表明大鼠后代存在胰岛素抵抗。这些结果与之前发表的数据一起表明,BPA 可以作为一种代谢紊乱化学物质。

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