Abstract
Local myostatin inhibition improves skeletal muscle glucose uptake in insulin-resistant high fat-diet-fed mice. Am J Physiol Endocrinol Metab 319: E163-E174, 2020. First published May 27, 2020; doi:10.1152/ajpendo. 00185.2019.-Myostatin inhibition is thought to improve whole body insulin sensitivity and mitigate the development of insulin resistance in models of obesity. However, although myostatin is known to be a major regulator of skeletal muscle mass, the direct effects of myostatin inhibition in muscle on glucose uptake and the mechanisms that may underlie this are still unclear. We investigated the effect of local myostatin inhibition by adeno-associated virus-mediated overexpression of the myostatin propeptide on insulin-stimulated skeletal muscle glucose disposal in chow-fed or high fat diet-fed mice and evaluated the molecular pathways that might mediate this. We found that myostatin inhibition improved glucose disposal in obese high fat diet-fed mice alongside the induction of muscle hypertrophy but did not have an impact in chow-fed mice. This improvement was not associated with greater glucose transporter or peroxisome proliferatoractivated receptor-γ coactivator-1α expression or 5= AMP-activated protein kinase activation as previously suggested. Instead, transcriptomic analysis suggested that the improvement in glucose disposal was associated with significant enrichment in genes involved in fatty acid metabolism and translation of mitochondrial genes. Thus, myostatin inhibition improves muscle insulin-stimulated glucose disposal in obese high fat diet-fed mice independent of muscle hypertrophy, potentially involving previously unidentified pathways.
| Original language | English |
|---|---|
| Pages (from-to) | E163-E174 |
| Journal | American Journal of Physiology - Endocrinology and Metabolism |
| Volume | 319 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jul 2020 |
Keywords
- Diabetes
- Glucose uptake
- Insulin resistance
- Myostatin
- Skeletal muscle
