The mitochondrial derived peptide MOTS c is a regulator of plasma metabolites and enhances insulin sensitivity
MOTS c is an exercise mimetic and improves insulin sensitivity in aged and diet induced obese mice. Although plasma markers are good markers for the metabolic condition, whether MOTS c changes plasma markers in diet induced obese mice has not been examined. Here, we used an unbiased metabolomics approach to examine the effect of MOTS c on plasma markers of metabolic dysfunction. We found that three pathways sphingolipid metabolism, monoacylglycerol metabolism, and dicarboxylate metabolism were reduced in MOTS c injected mice. Interestingly, these pathways are upregulated in obese and T2D models. MOTS c improves insulin sensitivity and increases beta oxidation to prevent fat accumulation in DIO mice through these pathways. These results provide us a better understanding of the mechanism of how MOTS c improves insulin sensitivity and reduces the body weight and fatty liver and opens a new venue for further study.
Physiological reports