Is irisin a human exercise gene?

Arising from P. Boström et al. Nature 481, 463–468 (2012)10.1038/nature10777 Boström et al. report that exercise training induces the expression of the FNDC5 gene in human muscle, producing irisin, which can convert white fat into brown fat, so enhancing metabolic uncoupling and hence caloric expenditure, and propose that this is a new health promoting hormone1. This assertion is based on experimental evidence that exogenous FNDC5 induces uncoupling protein 1 (UCP1) expression in white subcutaneous adipocytes; overexpression of FNDC5 in liver (elevating systemic irisin) prevents diet-induced weight gain and metabolic dysfunction and stimulates oxygen consumption in mice; and FNDC5 mRNA expression levels double after exercise training in eight human skeletal muscle samples. However, the UCP1 induction was lower than observed during Brite2 formation or the level associated with an improved diabetes profile in humans3. Here we demonstrate that muscle FNDC5 induction occurs only in a minority of subjects—whereas all types of exercise training programmes4,5,6,7, in the vast majority of people, yield some gain in cardiovascular or metabolic health, in our analysis of ∼200 subjects muscle FNDC5 was increased only in highly active elderly subjects, whereas FNDC5 expression was unrelated to metabolic status, which casts doubt over the general relevance of skeletal muscle FNDC5 to human health.