CONTEXT Metabolic inflexibility is a characteristic of insulin resistance, limiting the ability to transiently regulate oxidative metabolism and gene expression in response to nutrient availability. Little is known of the flexibility of post-transcriptional regulation, including circulatory miRNAs (c-miRNAs). DESIGN The abundances of targeted c-miRNAs, with reported functions in metabolic regulation, were analysed in response to a high-carbohydrate meal in healthy weight insulin-sensitive (IS) and overweight insulin-resistant (IR) women. PARTICIPANTS Age-matched healthy weight IS (n = 20, BMI = 24.3 ± 0.70) and overweight IR (n = 20, BMI = 28.6 ± 0.67) women. METHODS An abundance of c-miRNAs was quantified prior to and following a high-carbohydrate breakfast meal (2500 kJ; 50% carbohydrate, 20% fat and 27% protein). Target genes of the differentially regulated c-miRNA were measured in RNA extracted from circulatory peripheral blood mononuclear cells (PBMCs). RESULTS In healthy weight IS women, both miR-15a-5p (p = 0.03) and miR-17-5p (p < 0.01) levels were halved at 4 h post-meal. These miRNA remained unaltered following the same meal in the overweight IR women. Furthermore, amongst genes targeted by these miRNA, CPT1A (p = 0.01) and IL8 (p = 0.03) had also reduced expression 4 h post-meal only in the healthy weight IS women. CONCLUSIONS The study findings provide preliminary evidence for a possible extension of metabolic inflexibility to include c-miRNAs. TRIAL REGISTRATION The clinical trial is registered with Australian New Zealand Clinical Trials Registry under Trial registration: ANZCTR: ACTRN12615001108505. Registered on 21 October 2015.

中文翻译：

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在超重的胰岛素抵抗女性中，高碳水化合物膳食后血浆 miRNA 反应的不灵活。

背景代谢不灵活是胰岛素抵抗的一个特征，它限制了响应营养供应而瞬时调节氧化代谢和基因表达的能力。对转录后调节的灵活性知之甚少，包括循环 miRNA (c-miRNA)。设计针对健康体重胰岛素敏感 (IS) 和超重胰岛素抵抗 (IR) 女性的高碳水化合物膳食，分析了具有代谢调节功能的靶向 c-miRNA 的丰度。参与者年龄匹配的健康体重 IS (n = 20, BMI = 24.3 ± 0.70) 和超重 IR (n = 20, BMI = 28.6 ± 0.67) 女性。方法 在高碳水化合物早餐餐（2500 kJ；50% 碳水化合物、20% 脂肪和 27% 蛋白质）之前和之后对丰富的 c-miRNA 进行量化。在从循环外周血单核细胞 (PBMC) 中提取的 RNA 中测量差异调节的 c-miRNA 的靶基因。结果 在健康体重 IS 女性中，饭后 4 小时 miR-15a-5p (p = 0.03) 和 miR-17-5p (p < 0.01) 水平均减半。在超重的 IR 女性中，这些 miRNA 在同一餐后保持不变。此外，在这些 miRNA 靶向的基因中，CPT1A (p = 0.01) 和 IL8 (p = 0.03) 仅在健康体重 IS 女性中也降低了餐后 4 小时的表达。结论 研究结果为代谢不灵活性可能扩展到包括 c-miRNA 提供了初步证据。试验注册临床试验在澳大利亚新西兰临床试验注册处注册，试验注册：ANZCTR：ACTRN12615001108505。于 2015 年 10 月 21 日注册。