Adipose tissue parasite sequestration drives leptin production in mice and correlates with human cerebral malaria

Mejia, P. et al. (2021) Adipose tissue parasite sequestration drives leptin production in mice and correlates with human cerebral malaria. Science Advances, 7(13), eabe2484. (doi: 10.1126/sciadv.abe2484) (PMID:33762334) (PMCID:PMC7990332)

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Abstract

Circulating levels of the adipokine leptin are linked to neuropathology in experimental cerebral malaria (ECM), but its source and regulation mechanism remain unknown. Here, we show that sequestration of infected red blood cells (iRBCs) in white adipose tissue (WAT) microvasculature increased local vascular permeability and leptin production. Mice infected with parasite strains that fail to sequester in WAT displayed reduced leptin production and protection from ECM. WAT sequestration and leptin induction were lost in CD36KO mice; however, ECM susceptibility revealed sexual dimorphism. Adipocyte leptin was regulated by the mechanistic target of rapamycin complex 1 (mTORC1) and blocked by rapamycin. In humans, although Plasmodium falciparum infection did not increase circulating leptin levels, iRBC sequestration, tissue leptin production, and mTORC1 activity were positively correlated with CM in pediatric postmortem WAT. These data identify WAT sequestration as a trigger for leptin production with potential implications for pathogenesis of malaria infection, prognosis, and treatment.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Marti, Professor Matthias and De Niz, Dr Mariana
Authors: Mejia, P., Treviño-Villarreal, J. H., De Niz, M., Meibalan, E., Longchamp, A., Reynolds, J. S., Turnbull, L. B., Opoka, R. O., Roussilhon, C., Spielmann, T., Ozaki, C. K., Heussler, V. T., Seydel, K. B., Taylor, T. E., John, C. C., Milner, D. A., Marti, M., and Mitchell, J. R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Science Advances
Publisher:American Association for the Advancement of Science
ISSN:2375-2548
ISSN (Online):2375-2548
Published Online:24 March 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Science Advances 7(13): eabe2484
Publisher Policy:Reproduced under a Creative Commons License
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
172897BoneMalarMatthias MartiEuropean Research Council (ERC)682360III - Parasitology