Zhou Liyuan, Li Shunhua, Zhang Qian, Yu Miao, Xiao Xinhua
Key Laboratory of Endocrinology, Department of Endocrinology, Translational Medicine Center, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Front Nutr. 2022 Mar 1;9:853197. doi: 10.3389/fnut.2022.853197. eCollection 2022.
Detrimental exposures in mothers are recognized as risk factors for the development of metabolic dysfunction in offspring. In contrast, maternal exercise has been reported to be an effective strategy to maintain offspring health. However, the mechanisms underlying the protective effects of maternal exercise on adult offspring metabolic homeostasis are largely unclear. This study aims to investigate whether maternal exercise before and during pregnancy could combat the adverse effects of maternal high-fat diet (HFD) on metabolism in 24-week-old male offspring and to explore the role of miRNAs in mediating the effects. Female C57BL/6 mice were fed with either control diet or HFD 3-week prior to breeding and throughout pregnancy and lactation, among whom half of the HFD-fed mice were submitted to voluntary wheel running training 3-week before and during pregnancy. Male offspring were sedentary and fed with a control diet from weaning to 24 weeks. Body weight, the content of inguinal subcutaneous adipose tissue and perirenal visceral adipose tissue, glucose tolerance, and serum insulin and lipids in offspring were analyzed. Hepatic tissues were collected for transcriptome and miRNA sequencing and reverse transcription-quantitative polymerase chain reaction validation. The results showed that maternal HFD resulted in significant glucose intolerance, insulin resistance, and dyslipidemia in adult offspring, which were negated by maternal exercise. Transcriptome sequencing showed that maternal exercise reversed perinatal HFD-regulated genes in adult offspring, which were enriched in glucose and lipid metabolic-related signaling pathways. At the same time, maternal exercise significantly rescued the changes in the expression levels of 3 hepatic miRNAs in adult offspring, and their target genes were involved in the regulation of cholesterol biosynthesis and epigenetic modification, which may play an important role in mediating the intergenerational metabolic regulation of exercise. Overall, our research pioneered the role of miRNAs in mediating the programming effects of maternal exercise on adult offspring metabolism, which might provide novel insight into the prevention and treatment of metabolic disorders in early life.
母亲接触有害因素被认为是后代发生代谢功能障碍的风险因素。相比之下，有报道称母亲运动是维持后代健康的有效策略。然而，母亲运动对成年后代代谢稳态的保护作用背后的机制在很大程度上尚不清楚。本研究旨在调查孕期前后母亲运动是否可以对抗母亲高脂饮食（HFD）对24周龄雄性后代代谢的不利影响，并探讨miRNA在介导这些影响中的作用。雌性C57BL/6小鼠在繁殖前3周以及整个怀孕和哺乳期喂食对照饮食或HFD，其中一半喂食HFD的小鼠在怀孕前3周和怀孕期间进行自愿轮转跑步训练。雄性后代不运动，从断奶到24周喂食对照饮食。分析了后代的体重、腹股沟皮下脂肪组织和肾周内脏脂肪组织的含量、葡萄糖耐量以及血清胰岛素和脂质。收集肝脏组织进行转录组和miRNA测序以及逆转录定量聚合酶链反应验证。结果表明，母亲HFD导致成年后代出现明显的葡萄糖不耐受、胰岛素抵抗和血脂异常，而母亲运动可消除这些影响。转录组测序表明，母亲运动逆转了成年后代围产期HFD调节的基因，这些基因富集于葡萄糖和脂质代谢相关信号通路。同时，母亲运动显著挽救了成年后代肝脏中3种miRNA表达水平的变化，其靶基因参与胆固醇生物合成和表观遗传修饰的调节，这可能在介导运动的代际代谢调节中起重要作用。总体而言，我们的研究首次揭示了miRNA在介导母亲运动对成年后代代谢的编程效应中的作用，这可能为早期生活中代谢紊乱的预防和治疗提供新的见解。
