Effects of cell-type specific leptin receptor mutation on leptin transport across the BBB

► Generation and characterization of ELKO and ALKO mice for the first time. ► Illustrating that membrane-bound mutant receptors without signaling functions can mediate leptin transport across the BBB. ► Leptin signaling may hinder its own transport across endothelial barrier. ► Astrocytic leptin receptors do not play a crucial role in basal level leptin transport. ► Implications for obesity, metabolic syndrome, and neuroinflammation.