Mejia, Pedro; Treviño-Villarreal, J Humberto; De Niz, Mariana; Meibalan, Elamaran; Longchamp, Alban; Reynolds, Justin S; Turnbull, Lindsey B; Opoka, Robert O; Roussilhon, Christian; Spielmann, Tobias; Ozaki, C Keith; Heussler, Volker T.; Seydel, Karl B; Taylor, Terrie E; John, Chandy C; Milner, Danny A; Marti, Matthias; Mitchell, James R (2021). Adipose tissue parasite sequestration drives leptin production in mice and correlates with human cerebral malaria. Science Advances, 7(13) American Association for the Advancement of Science 10.1126/sciadv.abe2484
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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: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
08 Faculty of Science > Department of Biology > Institute of Cell Biology > Malaria 08 Faculty of Science > Department of Biology > Institute of Cell Biology |
Graduate School: |
Graduate School for Cellular and Biomedical Sciences (GCB) |
UniBE Contributor: |
Heussler, Volker |
Subjects: |
500 Science > 570 Life sciences; biology |
ISSN: |
2375-2548 |
Publisher: |
American Association for the Advancement of Science |
Funders: |
[42] Schweizerischer Nationalfonds |
Language: |
English |
Submitter: |
Volker Heussler |
Date Deposited: |
23 Apr 2021 11:44 |
Last Modified: |
05 Dec 2022 15:50 |
Publisher DOI: |
10.1126/sciadv.abe2484 |
PubMed ID: |
33762334 |
BORIS DOI: |
10.48350/155193 |
URI: |
https://boris.unibe.ch/id/eprint/155193 |
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