Agradecimentos: This work was supported by grants from the National Institutes of Health (Health (R01DK111529, R01DK106076, and R01DK123002 to Y.B.K.) and the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2022R1A2C1013479 to J.A.S.). K.C.R. is a recipient of São Paulo Research Foundation from Brazil (FAPESP 2019/19938-5). We thank Brad Lowell for providing tdTomato mice; Thomas Willnow for providing LRP2 floxed mice; Wei Zheng for providing rat choroid plexus cell line Z310; Navinci for providing the PLA kits, Thiago Araujo for technical help and Brad Lowell, Barbara Kahn, Mark Anderson, all members of the Kim lab for their helpful advice and discussion. We are grateful to the Histology Core at Beth Israel Deaconess Medical Center Ver menos

Abstract: Adipocyte-derived leptin enters the brain to exert its anorexigenic action, yet its transport mechanism is poorly understood. Here we report that LRP1 (low-density lipoprotein receptor-related protein-1) mediates the transport of leptin across the blood-CSF barrier in Foxj1 expressing cells highly enriched at the choroid plexus (ChP), coupled with the short-form leptin receptor, and LRP1 deletion from ependymocytes and ChP cells leads to leptin resistance and hyperphagia, causing obesity. Thus, LRP1 in epithelial cells is a principal regulator of leptin transport in the brain Ver menos