Diet-MEF2 interactions shape lipid droplet diversification in muscle to influence Drosophila lifespan.,Aging Cell

当前位置： X-MOL 学术 › Aging Cell › 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.)

Diet-MEF2 interactions shape lipid droplet diversification in muscle to influence Drosophila lifespan.
Aging Cell ( IF 8.0 ) Pub Date : 2020-06-14 , DOI: 10.1111/acel.13172
Xiao Zhao ₁ , Xiaotong Li ₁ , Xiangyu Shi ₁ , Jason Karpac ₁

Affiliation

The number, size, and composition of lipid droplets can be influenced by dietary changes that shift energy substrate availability. This diversification of lipid droplets can promote metabolic flexibility and shape cellular stress responses in unique tissues with distinctive metabolic roles. Using Drosophila, we uncovered a role for myocyte enhancer factor 2 (MEF2) in modulating diet‐dependent lipid droplet diversification within adult striated muscle, impacting mortality rates. Muscle‐specific attenuation of MEF2, whose chronic activation maintains glucose and mitochondrial homeostasis, leads to the accumulation of large, cholesterol ester‐enriched intramuscular lipid droplets in response to high calorie, carbohydrate‐sufficient diets. The diet‐dependent accumulation of these lipid droplets also correlates with both enhanced stress protection in muscle and increases in organismal lifespan. Furthermore, MEF2 attenuation releases an antagonistic regulation of cell cycle gene expression programs, and up‐regulation of Cyclin E is required for diet‐ and MEF2‐dependent diversification of intramuscular lipid droplets. The integration of MEF2‐regulated gene expression networks with dietary responses thus plays a critical role in shaping muscle metabolism and function, further influencing organismal lifespan. Together, these results highlight a potential protective role for intramuscular lipid droplets during dietary adaptation.

中文翻译：

饮食-MEF2 相互作用塑造肌肉中的脂滴多样化，从而影响果蝇的寿命。

脂滴的数量、大小和组成可能会受到饮食变化的影响，从而改变能量底物的可用性。脂滴的这种多样化可以促进代谢灵活性，并在具有独特代谢作用的独特组织中塑造细胞应激反应。利用果蝇，我们发现了肌细胞增强因子 2 (MEF2) 在调节成体横纹肌内饮食依赖性脂滴多样化、影响死亡率方面的作用。 MEF2 的肌肉特异性减弱，其慢性激活可维持葡萄糖和线粒体稳态，导致大量富含胆固醇酯的肌内脂滴积累，以响应高热量、碳水化合物充足的饮食。这些脂滴的饮食依赖性积累也与肌肉应激保护的增强和生物体寿命的延长相关。此外，MEF2 减弱会释放细胞周期基因表达程序的拮抗调节，并且细胞周期蛋白 E 的上调是饮食和 MEF2 依赖性肌内脂滴多样化所必需的。因此，MEF2 调控的基因表达网络与饮食反应的整合在塑造肌肉代谢和功能方面发挥着关键作用，进一步影响有机体的寿命。总之，这些结果凸显了肌内脂滴在饮食适应过程中的潜在保护作用。

更新日期：2020-06-14

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11