Considering the suspected dual impact of obesity on Kiss1 neurons (3), with initial over activation followed by long-term suppression, our data suggest that this astrocyte regulatory circuit, parallel to the direct effects of kisspeptins on GnRH neurons, contributes to adaptive responses of the reproductive axis to obesogenic stressors, both during puberty and adulthood, mainly in females. This evidence concerns the gene KISS1 and obesity due to melanocortin 4 receptor deficiency.