LRP1 mediates leptin transport by coupling with the short-form leptin receptor in the choroid plexus

Aykut Göktürk Üner; Won‐Mo Yang; Mincheol Kang; Kellen Cristina da Cruz Rodrigues; Ahmet Aydogan; Ji A Seo; Natália Ferreira Mendes; Min‐Seon Kim; Fatima Ezzahra Timzoura; Michael J. Holtzman; Maria K. Lehtinen; Vincent Prévot; Young‐Bum Kim

doi:10.1101/2023.07.03.547520

NeurosciencebioRxivJul 3, 2023

Preprint

LRP1 mediates leptin transport by coupling with the short-form leptin receptor in the choroid plexus

Aykut Göktürk Üner iD, Won‐Mo Yang iD, Mincheol Kang iD, Kellen Cristina da Cruz Rodrigues iD, Ahmet Aydogan, Ji A Seo iD, Natália Ferreira Mendes iD, Min‐Seon Kim iD, Fatima Ezzahra Timzoura iD, Michael J. Holtzman iD, Maria K. Lehtinen iD, Vincent Prévot iD, Young‐Bum Kim iD

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.

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