Adipocyte lipolysis protects mice against Trypanosoma brucei infection

Henrique Machado; Peter Hofer; Rudolf Zechner; Terry K Smith; Luísa M Figueiredo

doi:10.1038/s41564-023-01496-7

Adipocyte lipolysis protects mice against Trypanosoma brucei infection

Henrique Machado, Peter Hofer, Rudolf Zechner, Terry K Smith, Luísa M Figueiredo^*

^*Corresponding author for this work

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

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Abstract

Trypanosoma brucei causes African trypanosomiasis, colonizing adipose tissue and inducing weight loss. Here we investigated the molecular mechanisms responsible for adipose mass loss and its impact on disease pathology. We found that lipolysis is activated early in infection. Mice lacking B and T lymphocytes fail to upregulate adipocyte lipolysis, resulting in higher fat mass retention. Genetic ablation of the rate-limiting adipose triglyceride lipase specifically from adipocytes (Adipoq^Cre/+-Atgl^fl/fl) prevented the stimulation of adipocyte lipolysis during infection, reducing fat mass loss. Surprisingly, these mice succumbed earlier and presented a higher parasite burden in the gonadal adipose tissue, indicating that host lipolysis limits parasite growth. Consistently, free fatty acids comparable with those of adipose interstitial fluid induced loss of parasite viability. Adipocyte lipolysis emerges as a mechanism controlling local parasite burden and affecting the loss of fat mass in African trypanosomiasis.

Original language	English
Pages (from-to)	2020-2032
Number of pages	27
Journal	Nature Microbiology
Volume	8
DOIs	https://doi.org/10.1038/s41564-023-01496-7
Publication status	Published - 12 Oct 2023

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title = "Adipocyte lipolysis protects mice against Trypanosoma brucei infection",

abstract = "Trypanosoma brucei causes African trypanosomiasis, colonizing adipose tissue and inducing weight loss. Here we investigated the molecular mechanisms responsible for adipose mass loss and its impact on disease pathology. We found that lipolysis is activated early in infection. Mice lacking B and T lymphocytes fail to upregulate adipocyte lipolysis, resulting in higher fat mass retention. Genetic ablation of the rate-limiting adipose triglyceride lipase specifically from adipocytes (AdipoqCre/+-Atglfl/fl) prevented the stimulation of adipocyte lipolysis during infection, reducing fat mass loss. Surprisingly, these mice succumbed earlier and presented a higher parasite burden in the gonadal adipose tissue, indicating that host lipolysis limits parasite growth. Consistently, free fatty acids comparable with those of adipose interstitial fluid induced loss of parasite viability. Adipocyte lipolysis emerges as a mechanism controlling local parasite burden and affecting the loss of fat mass in African trypanosomiasis.",

author = "Henrique Machado and Peter Hofer and Rudolf Zechner and Smith, {Terry K} and Figueiredo, {Lu{\'i}sa M}",

note = "This work was supported by European Research Council (ERC) under the European Union{\textquoteright}s Horizon 2020 research and innovation programme (grant agreement no. 771714), Funda{\c c}{\~a}o para a Ci{\^e}ncia e Tecnologia (PD/BD/128286/2017 to H.M., CEECINST/00110/2018 to L.M.F.), the Austrian Fonds zur F{\"o}rderung der Wissenschaftlichen Forschung (F73 SFB Lipid Hydrolysis to R.Z.) and the Louis Jeantet Prize 2015 by the Fondation Louis Jeantet to R.Z.",

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AU - Machado, Henrique

AU - Hofer, Peter

AU - Zechner, Rudolf

AU - Smith, Terry K

AU - Figueiredo, Luísa M

N1 - This work was supported by European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 771714), Fundação para a Ciência e Tecnologia (PD/BD/128286/2017 to H.M., CEECINST/00110/2018 to L.M.F.), the Austrian Fonds zur Förderung der Wissenschaftlichen Forschung (F73 SFB Lipid Hydrolysis to R.Z.) and the Louis Jeantet Prize 2015 by the Fondation Louis Jeantet to R.Z.

PY - 2023/10/12

Y1 - 2023/10/12

N2 - Trypanosoma brucei causes African trypanosomiasis, colonizing adipose tissue and inducing weight loss. Here we investigated the molecular mechanisms responsible for adipose mass loss and its impact on disease pathology. We found that lipolysis is activated early in infection. Mice lacking B and T lymphocytes fail to upregulate adipocyte lipolysis, resulting in higher fat mass retention. Genetic ablation of the rate-limiting adipose triglyceride lipase specifically from adipocytes (AdipoqCre/+-Atglfl/fl) prevented the stimulation of adipocyte lipolysis during infection, reducing fat mass loss. Surprisingly, these mice succumbed earlier and presented a higher parasite burden in the gonadal adipose tissue, indicating that host lipolysis limits parasite growth. Consistently, free fatty acids comparable with those of adipose interstitial fluid induced loss of parasite viability. Adipocyte lipolysis emerges as a mechanism controlling local parasite burden and affecting the loss of fat mass in African trypanosomiasis.

AB - Trypanosoma brucei causes African trypanosomiasis, colonizing adipose tissue and inducing weight loss. Here we investigated the molecular mechanisms responsible for adipose mass loss and its impact on disease pathology. We found that lipolysis is activated early in infection. Mice lacking B and T lymphocytes fail to upregulate adipocyte lipolysis, resulting in higher fat mass retention. Genetic ablation of the rate-limiting adipose triglyceride lipase specifically from adipocytes (AdipoqCre/+-Atglfl/fl) prevented the stimulation of adipocyte lipolysis during infection, reducing fat mass loss. Surprisingly, these mice succumbed earlier and presented a higher parasite burden in the gonadal adipose tissue, indicating that host lipolysis limits parasite growth. Consistently, free fatty acids comparable with those of adipose interstitial fluid induced loss of parasite viability. Adipocyte lipolysis emerges as a mechanism controlling local parasite burden and affecting the loss of fat mass in African trypanosomiasis.

U2 - 10.1038/s41564-023-01496-7

DO - 10.1038/s41564-023-01496-7

M3 - Article

C2 - 37828246

SN - 2058-5276

VL - 8

SP - 2020

EP - 2032

JO - Nature Microbiology

JF - Nature Microbiology

ER -

Adipocyte lipolysis protects mice against Trypanosoma brucei infection

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