Browsing by Subject "FGF21"

This study investigates the metabolic consequences of a biomarker for mitochondrial myopathies, using the mouse as a model organism. The studied biomarker is fibroblast growth factor 21 (FGF21), which is secreted in high amounts from the diseased muscle tissue. It is an endocrine hormone that regulates lipid metabolism, and in healthy individuals it is mainly secreted from the liver. I utilized skeletal muscle samples from mice that were either wild type or had a mitochondrial myopathy, both with or without a whole-body knockout of FGF21. I analysed a data set from a targeted metabolomic experiment conducted on the skeletal muscle samples. The experiment was performed by our collaborator Vidya Velagapudi. Additionally I measured protein and mRNA expression of selected enzymes from the muscle samples. This study shows, that the cytokine FGF21 contributes to the disease progression of mitochondrial myopathy. The aspects of pathophysiology it regulates were all found to center on the metabolic pathway of one carbon (1C) metabolism. Serine de novo synthesis shuttles glucose carbons into 1C metabolism. The transsulfuration pathway produces glutathione using carbon units from the 1C pathway. The results of this study show, that FGF21 mediates the upregulation of alternative carbon donors in one carbon metabolism, especially serine biosynthesis, and the elevated utilisation of carbon units in the transsulfuration pathway. Not all of the metabolic changes characteristic of mitochondrial myopathy were affected by FGF21, e.g. the upregulation of acyl carnitines seen in mitochondrial myopathy was not affected by the knock-out of FGF21.