Importantly, Meg3 knockdown impaired systemic glucose homeostasis and insulin signaling in the liver, which can be restored by attenuating the cellular senescence of hepatic endothelium, indicating that cellular senescence of the vascular endothelium impairs glucose homeostasis and insulin signaling in obesity (Cheng et al., 2021). This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.