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mTORC2/Akt activation in adipocytes is required for adipose tissue inflammation in tuberculosis
BACKGROUND: Mycobacterium tuberculosis has co-evolved with the human host, adapting to exploit the immune system for persistence and transmission. While immunity to tuberculosis (TB) has been intensively studied in the lung and lymphoid system, little is known about the participation of adipose tiss...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6642333/ https://www.ncbi.nlm.nih.gov/pubmed/31279779 http://dx.doi.org/10.1016/j.ebiom.2019.06.052 |
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author | Martinez, Nuria Cheng, Catherine Y. Ketheesan, Natkunam Cullen, Aidan Tang, Yuefeng Lum, Josephine West, Kim Poidinger, Michael Guertin, David A. Singhal, Amit Kornfeld, Hardy |
author_facet | Martinez, Nuria Cheng, Catherine Y. Ketheesan, Natkunam Cullen, Aidan Tang, Yuefeng Lum, Josephine West, Kim Poidinger, Michael Guertin, David A. Singhal, Amit Kornfeld, Hardy |
author_sort | Martinez, Nuria |
collection | PubMed |
description | BACKGROUND: Mycobacterium tuberculosis has co-evolved with the human host, adapting to exploit the immune system for persistence and transmission. While immunity to tuberculosis (TB) has been intensively studied in the lung and lymphoid system, little is known about the participation of adipose tissues and non-immune cells in the host-pathogen interaction during this systemic disease. METHODS: C57BL/6J mice were aerosol infected with M. tuberculosis Erdman and presence of the bacteria and the fitness of the white and brown adipose tissues, liver and skeletal muscle were studied compared to uninfected mice. FINDINGS: M. tuberculosis infection in mice stimulated immune cell infiltration in visceral, and brown adipose tissue. Despite the absence of detectable bacterial dissemination to fat tissues, adipocytes produced localized pro-inflammatory signals that disrupted adipocyte lipid metabolism, resulting in adipocyte hypertrophy. Paradoxically, this resulted in increased insulin sensitivity and systemic glucose tolerance. Adipose tissue inflammation and enhanced glucose tolerance also developed in obese mice after aerosol M. tuberculosis infection. We found that infection induced adipose tissue Akt signaling, while inhibition of the Akt activator mTORC2 in adipocytes reversed TB-associated adipose tissue inflammation and cell hypertrophy. INTERPRETATION: Our study reveals a systemic response to aerosol M. tuberculosis infection that regulates adipose tissue lipid homeostasis through mTORC2/Akt signaling in adipocytes. Adipose tissue inflammation in TB is not simply a passive infiltration with leukocytes but requires the mechanistic participation of adipocyte signals. |
format | Online Article Text |
id | pubmed-6642333 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-66423332019-07-23 mTORC2/Akt activation in adipocytes is required for adipose tissue inflammation in tuberculosis Martinez, Nuria Cheng, Catherine Y. Ketheesan, Natkunam Cullen, Aidan Tang, Yuefeng Lum, Josephine West, Kim Poidinger, Michael Guertin, David A. Singhal, Amit Kornfeld, Hardy EBioMedicine Research paper BACKGROUND: Mycobacterium tuberculosis has co-evolved with the human host, adapting to exploit the immune system for persistence and transmission. While immunity to tuberculosis (TB) has been intensively studied in the lung and lymphoid system, little is known about the participation of adipose tissues and non-immune cells in the host-pathogen interaction during this systemic disease. METHODS: C57BL/6J mice were aerosol infected with M. tuberculosis Erdman and presence of the bacteria and the fitness of the white and brown adipose tissues, liver and skeletal muscle were studied compared to uninfected mice. FINDINGS: M. tuberculosis infection in mice stimulated immune cell infiltration in visceral, and brown adipose tissue. Despite the absence of detectable bacterial dissemination to fat tissues, adipocytes produced localized pro-inflammatory signals that disrupted adipocyte lipid metabolism, resulting in adipocyte hypertrophy. Paradoxically, this resulted in increased insulin sensitivity and systemic glucose tolerance. Adipose tissue inflammation and enhanced glucose tolerance also developed in obese mice after aerosol M. tuberculosis infection. We found that infection induced adipose tissue Akt signaling, while inhibition of the Akt activator mTORC2 in adipocytes reversed TB-associated adipose tissue inflammation and cell hypertrophy. INTERPRETATION: Our study reveals a systemic response to aerosol M. tuberculosis infection that regulates adipose tissue lipid homeostasis through mTORC2/Akt signaling in adipocytes. Adipose tissue inflammation in TB is not simply a passive infiltration with leukocytes but requires the mechanistic participation of adipocyte signals. Elsevier 2019-07-04 /pmc/articles/PMC6642333/ /pubmed/31279779 http://dx.doi.org/10.1016/j.ebiom.2019.06.052 Text en © 2019 The Authors. Published by Elsevier B.V. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research paper Martinez, Nuria Cheng, Catherine Y. Ketheesan, Natkunam Cullen, Aidan Tang, Yuefeng Lum, Josephine West, Kim Poidinger, Michael Guertin, David A. Singhal, Amit Kornfeld, Hardy mTORC2/Akt activation in adipocytes is required for adipose tissue inflammation in tuberculosis |
title | mTORC2/Akt activation in adipocytes is required for adipose tissue inflammation in tuberculosis |
title_full | mTORC2/Akt activation in adipocytes is required for adipose tissue inflammation in tuberculosis |
title_fullStr | mTORC2/Akt activation in adipocytes is required for adipose tissue inflammation in tuberculosis |
title_full_unstemmed | mTORC2/Akt activation in adipocytes is required for adipose tissue inflammation in tuberculosis |
title_short | mTORC2/Akt activation in adipocytes is required for adipose tissue inflammation in tuberculosis |
title_sort | mtorc2/akt activation in adipocytes is required for adipose tissue inflammation in tuberculosis |
topic | Research paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6642333/ https://www.ncbi.nlm.nih.gov/pubmed/31279779 http://dx.doi.org/10.1016/j.ebiom.2019.06.052 |
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