MiR-125b-2 knockout increases high-fat diet-induced fat accumulation and insulin resistance

文献类型： 外文期刊

第一作者： Wei, Li-Min

作者： Wei, Li-Min;Sun, Rui-Ping;Dong, Tao;Liu, Jie;Chen, Ting;Zeng, Bin;Wu, Jia-Han;Luo, Jun-yi;Sun, Jia-Jie;Xi, Qian-Yun;Zhang, Yong-Liang;Wei, Li-Min;Sun, Rui-Ping

作者机构：

期刊名称：SCIENTIFIC REPORTS （ 影响因子：4.379； 五年影响因子：5.133 ）

ISSN： 2045-2322

年卷期： 2020 年 10 卷 1 期

页码：

收录情况： SCI

摘要： Obese individuals are more susceptible to comorbidities than individuals of healthy weight, including cardiovascular disease and metabolic disorders. MicroRNAs are a class of small and noncoding RNAs that are implicated in the regulation of chronic human diseases. We previously reported that miR-125b plays a critical role in adipogenesis in vitro. However, the involvement of miR-125b-2 in fat metabolism in vivo remains unknown. In the present study, miR-125b-2 knockout mice were generated using CRISPR/CAS9 technology, resulting in mice with a 7 bp deletion in the seed sequence of miR-125b-2. MiR-125b-2 knockout increased the weight of liver tissue, epididymal white fat and inguinal white fat. MiR-125b-2 knockout also increased adipocyte volume in HFD-induced obese mice, while there were no significant differences in body weight and feed intake versus mice fed a normal diet. Additionally, qRT-PCR and western blot analysis revealed that the expression of the miR-125b-2 target gene SCD-1 and fat synthesis-associated genes, such as PPAR gamma and C/EBP alpha, were significantly up-regulated in miR-125b-2KO mice (P<0.05). Moreover, miR-125b-2KO altered HFD-induced changes in glucose tolerance and insulin resistance. In conclusion, we show that miR-125b-2 is a novel potential target for regulating fat accumulation, and also a candidate target to develop novel treatment strategies for obesity and diabetes.

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