INS and obesity due to melanocortin 4 receptor deficiency: Notably, in mice, metabolic effects of orchidectomy are very minor or absent on a standard chow diet, but androgen deprivation can exacerbate adipose hypertrophy, glucose intolerance, insulin insensitivity, and systemic inflammation when fed a high-fat diet [211], suggesting that interactions between hormone changes with aging could synergize with diet and obesity to affect BBB disruption.