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

Pedro Mejia; J. Humberto Treviño-Villarreal; Mariana De Niz; Elamaran Meibalan; Alban Longchamp; Justin S. Reynolds; Lindsey B. Turnbull; Robert O. Opoka; Christian Roussilhon; Tobias Spielmann; C. Keith Ozaki; Volker T. Heussler; Karl B. Seydel; Terrie E. Taylor; Chandy C. John; Danny A. Milner; Matthias Marti; James R. Mitchell

doi:10.1126/sciadv.abe2484

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

Pedro Mejia^*, J. Humberto Treviño-Villarreal^*, Mariana De Niz, Elamaran Meibalan, Alban Longchamp, Justin S. Reynolds, Lindsey B. Turnbull, Robert O. Opoka, Christian Roussilhon, Tobias Spielmann, C. Keith Ozaki, Volker T. Heussler, Karl B. Seydel, Terrie E. Taylor, Chandy C. John, Danny A. Milner, Matthias Marti, James R. Mitchell

^*Corresponding author for this work

Cell & Developmental Biology

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

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.

Original language	English (US)
Article number	eabe2484
Journal	Science Advances
Volume	7
Issue number	13
DOIs	https://doi.org/10.1126/sciadv.abe2484
State	Published - Mar 2021

ASJC Scopus subject areas

General

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1126/sciadv.abe2484

Cite this

Mejia, P., Humberto Treviño-Villarreal, J., De Niz, M., Meibalan, E., Longchamp, A., Reynolds, J. S., Turnbull, L. B., Opoka, R. O., Roussilhon, C., Spielmann, T., Keith Ozaki, C., Heussler, V. T., Seydel, K. B., Taylor, T. E., John, C. C., Milner, D. A., Marti, M., & Mitchell, J. R. (2021). Adipose tissue parasite sequestration drives leptin production in mice and correlates with human cerebral malaria. Science Advances, 7(13), Article eabe2484. https://doi.org/10.1126/sciadv.abe2484

@article{e8f7c67f073943788513d487966edab4,

title = "Adipose tissue parasite sequestration drives leptin production in mice and correlates with human cerebral malaria",

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.",

author = "Pedro Mejia and {Humberto Trevi{\~n}o-Villarreal}, J. and {De Niz}, Mariana and Elamaran Meibalan and Alban Longchamp and Reynolds, {Justin S.} and Turnbull, {Lindsey B.} and Opoka, {Robert O.} and Christian Roussilhon and Tobias Spielmann and {Keith Ozaki}, C. and Heussler, {Volker T.} and Seydel, {Karl B.} and Taylor, {Terrie E.} and John, {Chandy C.} and Milner, {Danny A.} and Matthias Marti and Mitchell, {James R.}",

note = "Publisher Copyright: Copyright {\textcopyright} 2021 The Authors, some rights reserved.",

year = "2021",

month = mar,

doi = "10.1126/sciadv.abe2484",

language = "English (US)",

volume = "7",

journal = "Science Advances",

issn = "2375-2548",

publisher = "American Association for the Advancement of Science",

number = "13",

}

Mejia, P, Humberto Treviño-Villarreal, J, De Niz, M, Meibalan, E, Longchamp, A, Reynolds, JS, Turnbull, LB, Opoka, RO, Roussilhon, C, Spielmann, T, Keith Ozaki, C, Heussler, VT, Seydel, KB, Taylor, TE, John, CC, Milner, DA, Marti, M & Mitchell, JR 2021, 'Adipose tissue parasite sequestration drives leptin production in mice and correlates with human cerebral malaria', Science Advances, vol. 7, no. 13, eabe2484. https://doi.org/10.1126/sciadv.abe2484

TY - JOUR

T1 - Adipose tissue parasite sequestration drives leptin production in mice and correlates with human cerebral malaria

AU - Mejia, Pedro

AU - Humberto Treviño-Villarreal, J.

AU - De Niz, Mariana

AU - Meibalan, Elamaran

AU - Longchamp, Alban

AU - Reynolds, Justin S.

AU - Turnbull, Lindsey B.

AU - Opoka, Robert O.

AU - Roussilhon, Christian

AU - Spielmann, Tobias

AU - Keith Ozaki, C.

AU - Heussler, Volker T.

AU - Seydel, Karl B.

AU - Taylor, Terrie E.

AU - John, Chandy C.

AU - Milner, Danny A.

AU - Marti, Matthias

AU - Mitchell, James R.

PY - 2021/3

Y1 - 2021/3

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85103485392&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85103485392&partnerID=8YFLogxK

U2 - 10.1126/sciadv.abe2484

DO - 10.1126/sciadv.abe2484

M3 - Article

C2 - 33762334

AN - SCOPUS:85103485392

SN - 2375-2548

VL - 7

JO - Science Advances

JF - Science Advances

IS - 13

M1 - eabe2484

ER -

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

Abstract

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this