FOXO3 and obesity due to melanocortin 4 receptor deficiency: Another study conducted in rats found that obesity accelerates ovarian follicle development and follicle loss in rats, while caloric restriction prolonged ovary lifespan by SIRT1/FOXO3a/NRF1-SIRT6 pathway (Wang et al., 2014), indicating the target of FOXO3 in follicle development.