Expanding the previous knowledge that brain ER stress underlies neurodegenerative diseases [95], recent studies have causally linked brain ER stress to the development of metabolic syndrome and related disorders such as overeating, obesity, leptin resistance, insulin resistance, β cell dysfunction, and hypertension [34;39; 42;104;105] under conditions of overnutrition [34;42] and related inflammatory insults [105]. This evidence concerns the gene LEP and overnutrition.