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

Details

Serval ID
serval:BIB_8FBCA28178E7
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Adipose tissue parasite sequestration drives leptin production in mice and correlates with human cerebral malaria.
Journal
Science advances
Author(s)
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., Mitchell J.R.
ISSN
2375-2548 (Electronic)
ISSN-L
2375-2548
Publication state
Published
Issued date
03/2021
Peer-reviewed
Oui
Volume
7
Number
13
Pages
eabe2484
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
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.
Pubmed
Web of science
Open Access
Yes
Create date
27/03/2021 16:51
Last modification date
10/04/2021 6:33
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