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.

doi:10.1101/2023.07.03.547520

bioRxiv · 10.1101/2023.07.03.547520

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.

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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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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. LRP1 mediates leptin transport by coupling with the short-form leptin receptor in the choroid plexus. https://doi.org/10.1101/2023.07.03.547520

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