Paternal high-fat diet and exercise regulate sperm miRNA and histone methylation to modify placental inflammation, nutrient transporter mRNA expression and fetal weight in a sex-dependent manner
Paternal high-fat diet and exercise regulate sperm miRNA and histone methylation to modify placental inflammation, nutrient transporter mRNA expression and fetal weight in a sex-dependent manner
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DOI：
10.1016/j.jnutbio.2020.108373
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发表时间：
2020-07-01
影响因子：
5.6
通讯作者：
Roemmich, James N.
中科院分区：
文献类型：
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作者：
Claycombe-Larson, Kate G.;Bundy, Amy N.;Roemmich, James N.
我们之前已经证明，与喂养高脂肪 (HF) 饮食且保持久坐的父亲相比，父亲 (F0) 喂养高脂肪 (HF) 饮食且锻炼的男性后代 (F1) 具有更强的骨骼肌胰岛素信号传导，并降低 2 型糖尿病 (T2DM) 风险。目前的研究扩展了这项工作，假设 F0 HF 饮食和运动通过精子 miRNA 表达的变化改变胎盘组织生长来调节 F1 T2DM 风险。为了测试这些假设，3 周大的雄性 C57BL/6 小鼠被喂食正常脂肪饮食（16% 脂肪）或 HF 饮食（45% 脂肪），并被分配进行为期 3 个月的自愿轮跑运动或笼内活动。结果显示，父亲运动导致 F0 精子 miRNA 193b 表达降低，而 miRNA 204 表达增加。 F0 HF 饮食可降低二甲基化组蛋白 3 赖氨酸 9 的蛋白质表达。 F1 雄性中 F0 HF 饮食降低了胎盘和胎儿组织重量。仅在 F1 雌性胎盘中，胎盘白介素 1 β 和肿瘤坏死因子 (TNF) α mRNA 表达因父方运动而降低，而营养转运蛋白 mRNA 表达因父方 HF 饮食而降低。用 miRNA 193b 处理原代胎盘细胞可抑制 TNF-α mRNA 表达，而 TNF-α 处理可降低 SLC38a2 mRNA 表达。此外，父亲的运动增加了雌性后代断奶时的体重。这些结果表明，胎盘组织重量、胎盘营养转运蛋白基因表达和胎儿体重会因父亲运动而改变，而子代的胎盘炎症基因表达会以性别特异性方式受到父亲运动的影响。由爱思唯尔公司出版
We previously have shown that male offspring (F1) of fathers (F0) fed a high-fat (HF) diet and that exercised had greater skeletal muscle insulin signaling and reduced type 2 diabetes mellitus (T2DM) risk compared to fathers fed HF diet and that remained sedentary. The current study extends this work by hypothesizing that F0 HF diet and exercise regulate F1 T2DM risk by alterations in placental tissue growth via changes in sperm miRNA expression. To test these hypotheses, 3-week-old male C57BL/6 mice were fed a normal-fat diet (16% fat) or an HF diet (45% fat) and assigned to either voluntary wheel running exercise or cage activity for 3 months. Results showed that F0 sperm miRNA 193b expression was decreased while miRNA 204 was increased by paternal exercise. Protein expression of dimethylated histone 3 lysine 9 was decreased with F0 HF diet. Placental and fetal tissue weights were decreased by F0 HF diet in F1 males. Placental interleukin-1 beta and tumor necrosis factor (TNF)-alpha mRNA expression was reduced by paternal exercise, while nutrient transporter mRNA expression was decreased by paternal HF diet only in the placentae of F1 females. Treatment of primary placental cell with miRNA 193b inhibited TNF-alpha mRNA expression, and treatment of TNF-alpha decreased SLC38a2 mRNA expression. Moreover, paternal exercise increased body weight at weaning in a female offspring. These results demonstrate that placental tissue weight, placental nutrient transporter gene expression and fetal weights are altered by paternal exercise, while placental inflammatory gene expression is influenced by paternal exercise in offspring in a sex-specific manner. Published by Elsevier Inc.