Conclusions
These results identify a novel crosstalk signaling pathway between adipose tissue and skeletal muscle in the development of insulin resistance, and indicate that adipose tissue-derived miR-27a may play a key role in the development of obesity-triggered insulin resistance in skeletal muscle.
Methods
The association between miR-27a and insulin resistance in skeletal muscle was determined in obese children, high-fat diet-induced miR-27a knockdown obese mice, db/db mice and C2C12 cells overexpressing miR-27a. The crosstalk mediated by exosomal miR-27a between adipose tissue and skeletal muscle was determined in C2C12 cells incubated with conditioned medium prepared from palmitate-treated 3T3-L1 adipocytes.
Results
We showed that serum miR-27a level correlated positively with obesity and insulin resistance in obese children, and that elevated serum miR-27a levels correlated with insulin resistance in leptin receptor-deficient db/db mice, and with obesity and insulin resistance in high-fat diet-fed C57BL/6J mice. MiR-27a released from adipocytes of high-fat diet-fed C57BL/6J mice was associated with triglyceride accumulation. MiR-27a derived from these adipocytes induced insulin resistance in C2C12 skeletal muscle cells through miR-27a-mediated repression of PPARγ and its downstream genes involved in the development of obesity. Conclusions: These results identify a novel crosstalk signaling pathway between adipose tissue and skeletal muscle in the development of insulin resistance, and indicate that adipose tissue-derived miR-27a may play a key role in the development of obesity-triggered insulin resistance in skeletal muscle.