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

Uner, A. A.; Yang, W.-M.; Kang, M.-C.; Rodrigues, K. C. d. C.; Aydogan, A.; Seo, J. A.; Mendes, N. F.; Kim, M.-S.; Timzoura, F. E.; Holtzman, M. J.; Lehtinen, M.; Prevot, V.; Kim, Y.-B.

2023-07-03 neuroscience
10.1101/2023.07.03.547520 bioRxiv
Show 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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