Department of Physiology and Pharmacology, Western University, London, Ontario N6A 5C1, Canada.
Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario L8S 4K1, Canada.
Toxicol Sci. 2018 Jul 1;164(1):72-84. doi: 10.1093/toxsci/kfy083.
Globally, approximately 10%-25% of women smoke during pregnancy. Since nicotine is highly addictive, women may use nicotine-containing products like nicotine replacement therapies for smoking cessation, but the long-term consequences of early life exposure to nicotine remain poorly defined. Our laboratory has previously demonstrated that maternal nicotine exposed (MNE) rat offspring exhibit hypertriglyceridemia due to increased hepatic de novo lipogenesis. Hypertriglyceridemia may also be attributed to impaired white adipose tissue (WAT) lipid storage; however, the effects of MNE on WAT are not completely understood. We hypothesize that nicotine-induced alterations in adipose function (eg, lipid storage) underlie dyslipidemia in MNE adults. Female 6-month-old rats exposed to nicotine during gestation and lactation exhibited significantly decreased visceral adipocyte cell area by 40%, attributed, in part, to a 3-fold increase in adipose triglyceride lipase (ATGL) protein expression compared with vehicle. Given ATGL has antioxidant properties and in utero nicotine exposure promotes oxidative stress in various tissues, we next investigated if there was evidence of increased oxidative stress in MNE WAT. At both 3 weeks and 6 months, MNE offspring expressed 37%-48% higher protein levels of superoxide dismutase-1 and -2 in WAT. Since oxidative stress can induce inflammation, we examined the inflammatory profile of WAT and found increased expression of cytokines (interleukin-1β, tumor necrosis factor α, and interleukin-6) by 44%-61% at 6 months. Collectively, this suggests that the expression of WAT ATGL may be induced to counter MNE-induced oxidative stress and inflammation. However, higher levels of ATGL would further promote lipolysis in WAT, culminating in impaired lipid storage and long-term dyslipidemia.
全球范围内,约有 10%-25%的女性在怀孕期间吸烟。由于尼古丁具有很强的成瘾性,女性可能会使用含有尼古丁的产品,如尼古丁替代疗法来戒烟,但早期接触尼古丁的长期后果仍不清楚。我们实验室之前的研究表明,母鼠尼古丁暴露(MNE)后代由于肝内从头脂肪生成增加而表现出高三酰甘油血症。高三酰甘油血症也可能归因于白色脂肪组织(WAT)脂质储存受损;然而,MNE 对 WAT 的影响尚不完全清楚。我们假设,尼古丁引起的脂肪功能(如脂质储存)改变是 MNE 成年人大血脂异常的基础。与对照组相比,在孕期和哺乳期暴露于尼古丁的 6 月龄雌性大鼠内脏脂肪细胞面积显著减少了 40%,部分原因是脂肪甘油三酯脂肪酶(ATGL)蛋白表达增加了 3 倍。鉴于 ATGL 具有抗氧化特性,并且宫内尼古丁暴露会促进各种组织中的氧化应激,我们接下来研究了 MNE WAT 是否有证据表明存在氧化应激增加。在 3 周和 6 个月时,MNE 后代的 WAT 中超氧化物歧化酶-1 和 -2 的蛋白水平分别升高了 37%-48%。由于氧化应激会引发炎症,我们检查了 WAT 的炎症特征,发现 6 个月时细胞因子(白细胞介素-1β、肿瘤坏死因子-α 和白细胞介素-6)的表达增加了 44%-61%。总之,这表明 WAT ATGL 的表达可能会被诱导来对抗 MNE 引起的氧化应激和炎症。然而,ATGL 水平的升高会进一步促进 WAT 中的脂肪分解,导致脂质储存受损和长期血脂异常。