GSE99803
RNAseq skeletal muscle FUNDC1-mKO mice
This experiment was conducted to identify mRNA transcripts alteration in muscle from skeletal muscle-sepcific Fundc1-knockout mice. The following abstract from the submitted manuscript describes the major findings of this work. Mitophagy directs muscle-adipose crosstalk to alleviate dietary obesity. Tingting Fu, Zhisheng Xu, Lin Liu, Qiqi Guo, Hao Wu, Xijun Liang, Danxia Zhou, Liwei Xiao, Lei Liu, Yong Liu, Min-Sheng Zhu, Quan Chen and Zhenji Gan. The quality of mitochondria in skeletal muscle is essential for maintaining metabolic homeostasis during adaptive stress responses. However, the precise control mechanism of muscle mitochondrial quality and its physiological impacts remain unclear. Here, we demonstrate that FUNDC1, a mediator of mitophagy, plays a critical role in controlling muscle mitochondrial quality as well as metabolic homeostasis. Skeletal muscle-specific ablation of FUNDC1 in mice resulted in LC3-mediated mitophagy defect, leading to impaired mitochondrial energetics. This caused decreased muscle fat utilization and endurance capacity during exercise. Interestingly, mice lacking muscle FUNDC1 were protected against high-fat diet-induced obesity with improved systemic insulin sensitivity and glucose tolerance despite reduced muscle mitochondrial energetics. Mechanistically, FUNDC1 deficiency elicited a retrograde response in muscle that upregulated FGF21 expression, thereby promoting the thermogenic remodeling of adipose tissue. Thus, these findings reveal a pivotal role of FUNDC1-dependent mitochondrial quality-control in mediating the muscle-adipose dialogue to regulate systemic metabolism. Overall design: Gastrocnemius muscle mRNA profiles of 8-week-old WT and FUNDC1-mKO mice were generated by deep sequencing, in replicate, using Illumina HiSeq 4000.