Despite its beneficial effects on metabolic profiles, clinical studies have consistently shown paradoxical upregulation of circulating ANGPTL6 in patients with metabolic disorders [16,17]; thus, similar to the mitokines FGF21 and GDF15, ANGPTL6 may also be considered a candidate biomarker reflecting a compensatory mechanism against metabolic stress. This evidence concerns the gene FGF21 and Other metabolic disease.