While previous reports demonstrate that PepT1 expression is decreased in enteroendocrine cells isolated from mice fed a HFD and that small intestinal PepT1 expression and function is decreased in rodent models of obesity and type 1 diabetes64–66, other studies have shown that PepT1 localization and activity at the brush-border membrane increases in rodent models of type 2 diabetes with hyperinsulinemia66,67. Here, SLC15A1 is linked to obesity due to melanocortin 4 receptor deficiency.