miR-378转基因小鼠脂肪组织的代谢表型分析

Metabolomics Phenotypes of Adipose Tissues from miR-378 Transgenic Mice

microRNA是一类小分子非编码RNA,参与调控多种生物学过程。该研究组前期工作中揭示了microRNA-378(miR-378)在脂肪组织中通过靶向硬脂酰CoA去饱和酶1(stearoyl-CoA desaturase 1, Scd1)调控脂分解。为了系统明确在脂肪组织中miR-378调控的代谢通路,该研究采用核磁共振技术分析了miR-378转基因小鼠和同窝野生型对照小鼠脂肪组织的代谢组差异。两种脂肪组织三个不同部位(棕色脂肪BAT、附睾旁白色脂肪gWAT、皮下白色脂肪iWAT)的代谢组学分析结果显示:miR-378转基因小鼠BAT中甘油磷酸胆碱、胆碱、丙二酸等代谢物含量更高;而gWAT脂肪组织中牛磺酸、丙二酸、次黄苷等代谢物含量更高;iWAT脂肪组织中牛磺酸、甘氨酸、谷氨酸、丙二酸等代谢物含量较高,而脂质、腺嘌呤核苷(adenine nucleoside, AMP)、二磷酸核苷(nucleoside diphosphate, ADP)及三磷酸核苷(nucleoside triphosphate, ATP)等代谢物含量较低。总体上, miR-378转基因小鼠脂肪组织中脂质含量减少,脂质分解作用及氨基酸代谢增强,整个机体的能量代谢增强。该研究结果揭示了miR-378对脂肪组织代谢具有重要调控作用。

microRNAs are small noncoding RNAs with profound physiological functions in regulating cellular metabolism,development and diseases.We have previously demonstrated that microRNA-378(miR-378)regulates lipolysis in adipose tissues by targeting stearoyl-CoA desaturase 1(Scd1).To further understand miR-378-mediated metabolic pathway(s)in adipose tissues,we analyzed the metabolic phenotypes of the adipose tissues from miR-378 transgenic mice(Tg)and wild type littermates(Wt)using the NMR-based metabonomics approach including brown adipose tissue(BAT),gonadal white adipose tissue(gWAT)and inguinal white adipose tissue(iWAT).The content of glycerophosphate choline,choline and malonic acid were higher in BAT adipose tissue from miR-378 Tg mice than that from Wt littermates.The content of taurine,malonic acid and hypoflavin were higher in gWAT adipose tissue from the Tg than that from Wt mice.The content of metabolites such as taurine,glycine,glutamic acid and malonic acid were higher,while lipid,adenine nucleoside(AMP),nucleoside diphosphate(ADP)and nucleoside triphosphate(ATP)were lower in iWAT adipose tissue of the Tg mice than that of Wt littermates.In general,we found that several lipid species were significantly reduced in miR-378 Tg mice compared to the Wt littermates,whereas lipolysis and amino acids metabolism were enhanced in the Tg mice compared to the Wt littermates.Together,our experimental data reveal that miR-378 plays important roles in regulating metabolisms of lipids and amino acids in adipose tissues.