As the duration of HFD exposure does not correspond with a full manifestation of leptin resistance67,68, these data indicate a surprising, albeit limited role for hindbrain astrocytes in leptin responsiveness in obesity, and moreover, suggest that a loss of leptin responsiveness in hindbrain astrocytes represents part of the maladaptive neuroregulatory response to obesity in rodents. Here, LEP is linked to obesity due to melanocortin 4 receptor deficiency.