Cg-Lepob/WiscJ ob/ob (BTBR ob/ob) mice with sustained hyperglycemia at less for 20 weeks, present anatomical alterations in the brain–blood barrier that provokes an ab-normal entry of leptin into the brain, with subsequent reduced central leptin signaling, indicating again the role of the brain in this metabolic disease [190]. The gene discussed is LEP; the disease is metabolic disease.