Plasma levels of both FGF21 [[37], [38], [39], [40], [41]] and GDF15 [[42], [43], [44]] are known to be increased in obese humans and rodents as well as in other metabolic disease states such as insulin resistance [45,46], NAFLD [[47], [48], [49], [50], [51], [52]] and mitochondrial disease [53,54]. This evidence concerns the gene GDF15 and Other metabolic disease.