GDF15 and metabolic disease: Our original interest in understanding GDF15 biology in the context of weight gain and metabolic disease related to three key observations: (i) GDF15 is elevated in human and rodent models of obesity [[42], [43], [44]]; (ii) transgenic overexpression or pharmacological treatment with GDF15, suppresses food intake and reduces body weight in mice [43,[84], [85], [86]]; and (iii) this effect is mediated exclusively via the hindbrain restricted expression of the GFRAL receptor [87,88].