Reynolds Leryn J, Chavan Niraj R, DeHoff Logan B, Preston Joshua D, Maddox Hannah F, O'Brien John M, Armstrong David A, Marsit Carmen J, Pearson Kevin J
Department of Human Movement Sciences, Old Dominion University, Norfolk, VA, USA.
Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY, USA.
Exp Physiol. 2019 Jan;104(1):93-99. doi: 10.1113/EP087307. Epub 2018 Nov 22.
What is the central question of this study? Is chemerin, an adipokine implicated in obesity, increased in neonates following in utero cigarette smoke exposure. What is the main finding and its importance? Chemerin mRNA expression was increased and chemerin DNA methylation was decreased in babies born to mothers who smoked during pregnancy. These data provide a potential mechanism that may be mediating the increased obesity risk in individuals that are born to mothers who smoked during pregnancy.
It has been shown that in utero tobacco exposure increases offspring risk for obesity, but the mechanisms responsible for this increased risk are not well understood. Chemerin is an adipokine that regulates adipocyte differentiation. This chemokine is elevated in obese individuals and with smoke exposure, but its levels have not been measured in neonates exposed to cigarette smoke in utero. We examined chemerin gene expression [n = 31 non-smoker (NS) and 15 smoker (S)] and DNA methylation (n = 28 NS and n = 11 S) in skin collected from babies born to mothers who smoked during pregnancy as compared to non-smoking controls. Quality RNA and DNA were isolated from foreskin tissue following circumcision, and chemerin gene expression and DNA methylation were assessed. Further, in a second cohort, we utilized primary dermal foreskin fibroblasts as a functional measure of adipogenesis in living cells (n = 11 NS and n = 8 S). Cells were stimulated with an adipogenic cocktail, mRNA was isolated from cells after 14 days, and chemerin gene expression assessed via real-time PCR. Chemerin mRNA was elevated in both whole tissue (NS: 2409.20 ± 555.28 counts and S: 2966.72 ± 636.84 counts; P < 0.01) and primary fibroblasts (NS: 1.12 ± and S: 2.13 ± ; P = 0.04) collected from infants born to smoking mothers. Chemerin DNA methylation was reduced in whole tissue of offspring born to smokers (NS: 4.18 ± 1.28 and S: 3.07 ± 1.31%; P = 0.02), which may contribute to the increased gene expression. Neonates born to mothers who smoke during pregnancy exhibit distinct changes in chemerin gene expression in response to in utero tobacco smoke exposure which are regulated in part by epigenetic alterations.
本研究的核心问题是什么？脂肪因子chemerin与肥胖有关，那么子宫内暴露于香烟烟雾的新生儿体内的chemerin是否增加？主要发现及其重要性是什么？孕期吸烟母亲所生婴儿的chemerin mRNA表达增加，chemerin DNA甲基化减少。这些数据提供了一种潜在机制，可能介导了孕期吸烟母亲所生孩子肥胖风险增加的现象。
已有研究表明，子宫内暴露于烟草会增加后代肥胖风险，但导致这种风险增加的机制尚不清楚。Chemerin是一种调节脂肪细胞分化的脂肪因子。这种趋化因子在肥胖个体中以及暴露于烟雾时会升高，但其在子宫内暴露于香烟烟雾的新生儿中的水平尚未测定。我们检测了孕期吸烟母亲所生婴儿与非吸烟对照婴儿的皮肤中chemerin基因表达（非吸烟者31例，吸烟者15例）和DNA甲基化（非吸烟者28例，吸烟者11例）情况。包皮环切术后从包皮组织中分离出高质量的RNA和DNA，并评估chemerin基因表达和DNA甲基化情况。此外，在第二个队列中，我们利用原代表皮包皮成纤维细胞作为活细胞中脂肪生成的功能指标（非吸烟者11例，吸烟者8例）。用脂肪生成混合剂刺激细胞，14天后从细胞中分离出mRNA，并通过实时PCR评估chemerin基因表达。孕期吸烟母亲所生婴儿的全组织（非吸烟者：2409.20±555.28计数，吸烟者：2966.72±636.84计数；P<0.01）和原代成纤维细胞（非吸烟者：1.12±，吸烟者：2.13±；P=0.04）中chemerin mRNA均升高。吸烟者所生孩子全组织中的chemerin DNA甲基化降低（非吸烟者：4.18±1.28，吸烟者：3.07±1.31%；P=0.02），这可能导致基因表达增加。孕期吸烟母亲所生新生儿对子宫内烟草烟雾暴露的反应表现为chemerin基因表达的明显变化，这部分受表观遗传改变的调控。
