Several studies have proposed serum fibroblast growth factor 21 (FGF21) levels as a sensitive biomarker of mitochondrial diseases. Serum FGF21 are the best predictor of these disorders when compared to serum levels of classical indicators: creatine kinase, lactate, pyruvate, and the lactate to pyruvate ratio.
Enhanced FGF21 production and circulation has been linked to the metabolic adaptation to starvation. Laeger and colleagues have shown in the Journal of Clinical Investigation that hepatic FGF21 expression is induced by dietary protein restriction, but not energy restriction. Circulating FGF21 was increased 10-fold in mice and rats fed a low-protein (LP) diet. In these animals, liver Fgf21 expression was increased within 24 hours of reduced protein intake. In humans, circulating FGF21 levels increased dramatically following 28 days on a LP diet. The authors showed that reduced protein intake underlies the increase in circulating FGF21 in response to starvation and a ketogenic diet and that FGF21 is required for behavioral and metabolic responses to protein restriction. FGF21 therefore represents an endocrine signal of protein restriction, which acts to coordinate metabolism and growth during periods of reduced protein intake. These novel data have to be considered when using FGF21 as a biomarker for diagnosis of patients with suspected mitochondrial diseases who might often be under protein restriction giving their feeding difficulties or under ketogenic diet.
Posted by Nicola Brunetti-Pierri