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-1β and tumor necrosis factor (TNF)-α 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-α mRNA expression, and treatment of TNF-α 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.

我们以前已经证明，与高脂饮食的父亲相比，高脂饮食的父亲（F0）的雄性后代（F1）和骨骼肌胰岛素信号传导更高的骨骼肌胰岛素信号传导和2型糖尿病（T2DM）风险降低。久坐不动。目前的研究通过假设F0 HF饮食和运动通过改变胎盘组织生长来调节F1 T2DM风险来扩展这项工作。精子miRNA表达的变化。为了检验这些假设，给3周大的雄性C57BL / 6小鼠喂食了正常脂肪饮食（16％脂肪）或HF饮食（45％脂肪），并进行了3个月的自愿轮转锻炼或笼养活动。结果显示，通过父亲运动，F0精子miRNA 193b表达降低，而miRNA 204升高。F0 HF饮食降低了二甲基化组蛋白3赖氨酸9的蛋白质表达。F1 HF饮食降低了F1男性的胎盘和胎儿组织重量。父本锻炼可降低胎盘白细胞介素-1β和肿瘤坏死因子（TNF）-αmRNA的表达，而父本HF饮食可降低F1雌性胎盘的营养转运蛋白mRNA表达。用miRNA 193b处理原代胎盘细胞可抑制TNF-αmRNA表达，和TNF-α的治疗降低了SLC38a2 mRNA的表达。此外，在雌性后代断奶时，父亲运动会增加体重。这些结果表明，父本运动改变了胎盘组织的重量，胎盘营养素转运蛋白的基因表达和胎儿的重量，而父本运动对胎盘的炎症基因表达产生了性别特异性的影响。