Laboratory of Endocrine Physiology, Department of Physiological Sciences, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, RJ, 20551-030, Brazil.
Laboratory of Metabolic Disorders, School of Applied Sciences, University of Campinas, Limeira, SP, 13484-350, Brazil.
Mol Cell Endocrinol. 2021 Mar 1;523:111141. doi: 10.1016/j.mce.2020.111141. Epub 2020 Dec 24.
In rats, maternal nicotine exposure during lactation induces obesity, thyroid dysfunction, brown adipose tissue (BAT) hypofunction and liver alterations in adult offspring. Both thyroid function and lipid metabolism are influenced by gene silencing mediated by microRNAs (miRNAs). Here we investigated long-term effects of early nicotine exposure on molecular and epigenetic mechanisms closely related to thyroid and lipid metabolism, through the expression of mRNAs and miRNAs in BAT and liver of adult male and female offspring. At postnatal day 2 (PND2), lactating control (CON) or nicotine (NIC) dams were subcutaneously implanted with osmotic minipumps containing, respectively, saline or 6 mg/kg nicotine. Litters were adjusted to 3 males and 3 females. Offspring's euthanasia occurred at PND180. In the BAT, NIC females showed higher Dio2 mRNA expression, while miR-382* expression was not altered in both sexes. In the liver, NIC offspring of both sexes showed lower Dio1 mRNA expression and higher miR-224 expression, while only NIC females had higher miR-383 and miR-21 expressions. NIC offspring of both sexes showed higher mRNA expression of SCD1 in the liver; NIC males had decreased CPT1 expression, whereas NIC females had increased FASN, miR-370 and miR-122 expressions. Regardless of sex, alterations in liver Dio1, miR-224 and SCD1 expressions are involved in the disturbances caused by maternal nicotine exposure during breastfeeding. Interestingly, females had more altered miRs in the liver. Early nicotine exposure induces a sex dimorphism, particularly regarding hepatic lipid metabolism, through miRs expression.
在大鼠中，哺乳期母体尼古丁暴露会导致成年后代肥胖、甲状腺功能障碍、棕色脂肪组织（BAT）功能低下和肝脏改变。甲状腺功能和脂质代谢都受 microRNAs（miRNAs）介导的基因沉默影响。在这里，我们通过 BAT 和成年雄性和雌性后代肝脏中 mRNAs 和 miRNAs 的表达，研究了早期尼古丁暴露对与甲状腺和脂质代谢密切相关的分子和表观遗传机制的长期影响。在产后第 2 天（PND2），哺乳期对照（CON）或尼古丁（NIC）母鼠皮下植入含有生理盐水或 6mg/kg 尼古丁的渗透微型泵。将幼崽调整为 3 只雄性和 3 只雌性。后代的安乐死发生在 PND180。在 BAT 中，NIC 雌性的 Dio2 mRNA 表达较高，而雌雄两性的 miR-382*表达均未改变。在肝脏中，雌雄两性的 NIC 后代 Dio1 mRNA 表达较低，miR-224 表达较高，而只有 NIC 雌性的 miR-383 和 miR-21 表达较高。雌雄两性的 NIC 后代肝脏 SCD1 mRNA 表达较高；NIC 雄性 CPT1 表达降低，而 NIC 雌性 FASN、miR-370 和 miR-122 表达增加。无论性别如何，哺乳期母体尼古丁暴露引起的 Dio1、miR-224 和 SCD1 表达的改变都与肝脏紊乱有关。有趣的是，雌性的肝脏中改变的 miRs 更多。早期尼古丁暴露通过 miR 表达诱导性别二态性，特别是在肝脏脂质代谢方面。
