FGF-21 is an atypical member of the fibroblast growth factor family, displaying pleitropic hormone-like metabolic regulation due to a lack of the heparin binding. FGF-21 signalling regulates glucose and lipid metabolism as its main function is believed to be an adaptive response to starvation, resulting in glucose uptake in adipose tissue, increased sensitivity to insulin, increased energy expenditure, fat utilisation and lipid excretion. FGF-21 has also been found to increase mitochondrial function, biogenesis and therefore energy. It is possible that the pseudo-starvation state induced by mitochondrial dysfunction in mitochondrial disease may result in an increased FGF-21 expression, in an effort to counteract the underlying metabolic deficiency.
We have found that serum FGF-21 levels as a sensitive biomarker of mitochondrial disease. After comparison to other classical biomarkers such as serum lactate and pyruvate, statistical analysis demonstrated that FGF-21 was the best measured parameter capable of predicting mitochondrial disease.