GDF15 and Anorexia: Here, using a transgenic mouse model of mitochondrial stress with compromised muscle‐specific OXPHOS capacity via respiratory uncoupling, we (i) demonstrate the induction and diurnal variation of GDF15 as a myokine, (ii) show that genetic ablation of GDF15 during mitochondrial stress prevents a systemic metabolic response, and (iii) provide mechanistic in vivo evidence for a GDF15‐dependent daytime‐restricted anorexia and metabolic flexibility.