bioRxivNeurosciencePreprint
LRP1 mediates leptin transport by coupling with the short-form leptin receptor in the choroid plexus
Aykut Göktürk ÜneriD, Won‐Mo YangiD, Mincheol KangiD, Kellen Cristina da Cruz RodriguesiD, Ahmet Aydogan, Ji A SeoiD, Natália Ferreira MendesiD, Min‐Seon KimiD, Fatima Ezzahra TimzouraiD, Michael J. HoltzmaniD, Maria K. LehtineniD, Vincent PrévotiD, Young‐Bum KimiD
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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