Loss of CrAT function might be central to metabolic disease considering that OXPHOS lag is synonymous with O2 deficit [16], and that muscle type III and IV afferents, which have been shown to promote central fatigue [104,105] and to limit top-end exercise performance [32,33], might fire prematurely due to metabolic inflexibility in obese individuals. The gene discussed is CRAT; the disease is metabolic disease.