The mechanisms through which obesity contributes to these changes are unknown, and maybe multifold instead of a singular mechanism, but some plausible candidates include systemic inflammation (51), the overactivation of microglia (52, 53), stress (54), microvascular changes, insulin resistance, hyperglycemia, plasticity related to lower mobility, or genetic predisposition to brain changes which increase the risk of obesity. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.