GSE174547
Vascular mitohormesis couples Mfn2 with improved systemic metabolism and healthspan
In this study, we hypothesized that mitochondrial dynamics in ECs orchestrates whole-body metabolic status. Here we report that genetic deficiency of endothelial Mfn2 (Mfn2i?EC) in mice, originated a mitohormetic response that caused favorable vascular adaptations with regards to antioxidant defenses, mitochondrial fitness and lipid oxidation. As a result, Mfn2i?EC mice exhibited improved metabolism, resistance to diet-induced obesity and delayed age-related decline. Our results reveal vascular mitohormesis as a novel operation mode influencing systemic energy metabolism and healthspan. These findings endorse the endothelium as a genuine metabolic organ and a potential target against metabolic and age-related deterioration. Overall design: RNAseq profiles of endothelial cells residing in the adipose tissue from Pdgfb-iCreERT2:Rpl22HA (endothelial RiboTag mice "WT" - 4 replicates) andPdgfb-iCreERT2:Mfn2i?EC:Rpl22HA (Mfn2i?EC:Rpl22HA) (endothelial RiboTag and endothelial Mfn2 deficient "KO" - 5 replicates) mice.