当前位置: X-MOL 学术EMBO Rep. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
miR-183 and miR-96 orchestrate both glucose and fat utilization in skeletal muscle
EMBO Reports ( IF 7.7 ) Pub Date : 2021-08-06 , DOI: 10.15252/embr.202052247
Hui Wang 1 , Mei Ma 1 , Yuying Li 1 , Jinxin Liu 2 , Chao Sun 1 , Shengnan Liu 1 , Yiruo Ma 1 , Ying Yan 1 , Zhili Tang 1 , Siyi Shen 1 , Jing Yu 1 , Yuting Wu 1 , Jingjing Jiang 3 , Li Wang 2 , Zi-Bing Jin 4 , Hao Ying 1, 5 , Yan Li 2
Affiliation  

Our knowledge of the coordination of fuel usage in skeletal muscle is incomplete. Whether and how microRNAs are involved in the substrate selection for oxidation is largely unknown. Here we show that mice lacking miR-183 and miR-96 have enhanced muscle oxidative phenotype and altered glucose/lipid homeostasis. Moreover, loss of miR-183 and miR-96 results in a shift in substrate utilization toward fat relative to carbohydrates in mice. Mechanistically, loss of miR-183 and miR-96 suppresses glucose utilization in skeletal muscle by increasing PDHA1 phosphorylation via targeting FoxO1 and PDK4. On the other hand, loss of miR-183 and miR-96 promotes fat usage in skeletal muscle by enhancing intramuscular lipolysis via targeting FoxO1 and ATGL. Thus, our study establishes miR-183 and miR-96 as master coordinators of fuel selection and metabolic homeostasis owing to their capability of modulating both glucose utilization and fat catabolism. Lastly, we show that loss of miR-183 and miR-96 can alleviate obesity and improve glucose metabolism in high-fat diet-induced mice, suggesting that miR-183 and miR-96 may serve as therapeutic targets for metabolic diseases.

中文翻译:

miR-183 和 miR-96 在骨骼肌中协调葡萄糖和脂肪的利用

我们对骨骼肌中燃料使用协调的了解是不完整的。microRNA是否以及如何参与氧化的底物选择在很大程度上是未知的。在这里,我们显示缺乏 miR-183 和 miR-96 的小鼠具有增强的肌肉氧化表型和改变的葡萄糖/脂质稳态。此外,miR-183 和 miR-96 的缺失导致小鼠底物利用相对于碳水化合物向脂肪的转变。从机制上讲,miR-183 和 miR-96 的缺失通过靶向 FoxO1 和 PDK4 增加 PDHA1 磷酸化来抑制骨骼肌中的葡萄糖利用。另一方面,miR-183 和 miR-96 的缺失通过靶向 FoxO1 和 ATGL 增强肌肉内脂肪分解来促进骨骼肌中的脂肪使用。因此,我们的研究将 miR-183 和 miR-96 确立为燃料选择和代谢稳态的主要协调者,因为它们具有调节葡萄糖利用和脂肪分解代谢的能力。最后,我们表明 miR-183 和 miR-96 的缺失可以减轻高脂饮食诱导的小鼠的肥胖并改善葡萄糖代谢,这表明 miR-183 和 miR-96 可以作为代谢疾病的治疗靶点。
更新日期:2021-09-06
down
wechat
bug