POLG mouse metabolic transcriptome

Here we report that mitochondrial mutations in the young, pre-progeroid polymerase gamma mutator (POLG) mouse cause an adaptive aerobic starvation-like response. As a result, these mice exhibit signs of metabolic imbalance. An unexpected benefit ofthis adaptive response is the complete resistance to diet-induced obesity when POLG mice are placed on a high-fat diet (HFD).Transcriptomic studies in liver and WAT identify a mechanistic link between FGF21, a long-known marker of mitochondrial disease,and systemic metabolic adaptation in response to mitochondrial stress.