Milk protein-derived peptides induce 5-HT2C-mediated satiety in vivo

This study investigates the ability of milk protein-derived peptides to specifically activate the serotonin 2C (5-HT2C) receptor, a key receptor in central regulation of food intake. A dose dependent 5-HT2C receptor activation by the 1 kDa ultrafiltration permeates of a sodium caseinate (NaCNH-1 kDa permeate) and a whey protein hydrolysate (WPH-1 kDa permeate) was demonstrated using an intracellular calcium mobilisation assay in human embryonic kidney (Hek) cells expressing the 5-HT2C receptor. Both samples activated the 5-HT2C but not the 5-HT2A and 5-HT2B receptors. NaCNH-1 kDa permeate significantly (p < 0.01) reduced cumulative food intake when administered to male mice (C57Bl/6) by intraperitoneal injection at 500 mg kg−1 body weight. In contrast, no effect of WPH-1 kDa permeate could be seen on food intake in vivo. These results demonstrate the promising appetite-suppressing potential of NaCN-derived peptides, targeting the 5-HT2C receptor.