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TACI-Deficient Macrophages Protect Mice Against Metaflammation and Obesity-Induced Dysregulation of Glucose Homeostasis

Transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) is a receptor for the TNF superfamily cytokines, B cell–activating factor (BAFF), and A proliferation–inducing ligand (APRIL). Here, we demonstrate that TACI-deficient mice subjected to high-fat diet (HFD) are pro...

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Autores principales: Liu, Lunhua, Inouye, Karen Etsuko, Allman, Windy Rose, Coleman, Adam Steven, Siddiqui, Shafiuddin, Hotamisligil, Gökhan Siddik, Akkoyunlu, Mustafa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054430/
https://www.ncbi.nlm.nih.gov/pubmed/29871859
http://dx.doi.org/10.2337/db17-1089
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author Liu, Lunhua
Inouye, Karen Etsuko
Allman, Windy Rose
Coleman, Adam Steven
Siddiqui, Shafiuddin
Hotamisligil, Gökhan Siddik
Akkoyunlu, Mustafa
author_facet Liu, Lunhua
Inouye, Karen Etsuko
Allman, Windy Rose
Coleman, Adam Steven
Siddiqui, Shafiuddin
Hotamisligil, Gökhan Siddik
Akkoyunlu, Mustafa
author_sort Liu, Lunhua
collection PubMed
description Transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) is a receptor for the TNF superfamily cytokines, B cell–activating factor (BAFF), and A proliferation–inducing ligand (APRIL). Here, we demonstrate that TACI-deficient mice subjected to high-fat diet (HFD) are protected from weight gain and dysregulated glucose homeostasis. Resistance to HFD-induced metabolic changes in TACI-deficient mice does not involve TACI-mediated adipogenesis. Instead, accumulation of M2 macrophages (Mϕs), eosinophils, and type 2 innate lymphoid cells in visceral adipose tissue (VAT) is implicated in the protection from obesity-induced assaults. In support of this hypothesis, adoptively transferred TACI-deficient peritoneal or adipose tissue Mϕs, but not B cells, can improve glucose metabolism in the obese host. Interestingly, the transferred TACI-deficient Mϕs not only home to host VAT but also trigger the accumulation of host M2 Mϕs and eosinophils in VAT. The increase in host M2 Mϕs in VAT is likely a result of eosinophil recruitment in response to eotaxin-2 produced by TACI-deficient Mϕs. Insulin signaling experiments revealed that IL-10 secreted by TACI-deficient Mϕs is responsible for maintaining adipocyte insulin sensitivity. Thus, the adoptive transfer experiments offer a model where TACI-deficient Mϕs accumulate in VAT and protect against metaflammation and obesity-associated dysregulation of glucose metabolism.
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spelling pubmed-60544302019-08-01 TACI-Deficient Macrophages Protect Mice Against Metaflammation and Obesity-Induced Dysregulation of Glucose Homeostasis Liu, Lunhua Inouye, Karen Etsuko Allman, Windy Rose Coleman, Adam Steven Siddiqui, Shafiuddin Hotamisligil, Gökhan Siddik Akkoyunlu, Mustafa Diabetes Immunology and Transplantation Transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) is a receptor for the TNF superfamily cytokines, B cell–activating factor (BAFF), and A proliferation–inducing ligand (APRIL). Here, we demonstrate that TACI-deficient mice subjected to high-fat diet (HFD) are protected from weight gain and dysregulated glucose homeostasis. Resistance to HFD-induced metabolic changes in TACI-deficient mice does not involve TACI-mediated adipogenesis. Instead, accumulation of M2 macrophages (Mϕs), eosinophils, and type 2 innate lymphoid cells in visceral adipose tissue (VAT) is implicated in the protection from obesity-induced assaults. In support of this hypothesis, adoptively transferred TACI-deficient peritoneal or adipose tissue Mϕs, but not B cells, can improve glucose metabolism in the obese host. Interestingly, the transferred TACI-deficient Mϕs not only home to host VAT but also trigger the accumulation of host M2 Mϕs and eosinophils in VAT. The increase in host M2 Mϕs in VAT is likely a result of eosinophil recruitment in response to eotaxin-2 produced by TACI-deficient Mϕs. Insulin signaling experiments revealed that IL-10 secreted by TACI-deficient Mϕs is responsible for maintaining adipocyte insulin sensitivity. Thus, the adoptive transfer experiments offer a model where TACI-deficient Mϕs accumulate in VAT and protect against metaflammation and obesity-associated dysregulation of glucose metabolism. American Diabetes Association 2018-08 2018-06-05 /pmc/articles/PMC6054430/ /pubmed/29871859 http://dx.doi.org/10.2337/db17-1089 Text en © 2018 by the American Diabetes Association. http://www.diabetesjournals.org/content/licenseReaders may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.
spellingShingle Immunology and Transplantation
Liu, Lunhua
Inouye, Karen Etsuko
Allman, Windy Rose
Coleman, Adam Steven
Siddiqui, Shafiuddin
Hotamisligil, Gökhan Siddik
Akkoyunlu, Mustafa
TACI-Deficient Macrophages Protect Mice Against Metaflammation and Obesity-Induced Dysregulation of Glucose Homeostasis
title TACI-Deficient Macrophages Protect Mice Against Metaflammation and Obesity-Induced Dysregulation of Glucose Homeostasis
title_full TACI-Deficient Macrophages Protect Mice Against Metaflammation and Obesity-Induced Dysregulation of Glucose Homeostasis
title_fullStr TACI-Deficient Macrophages Protect Mice Against Metaflammation and Obesity-Induced Dysregulation of Glucose Homeostasis
title_full_unstemmed TACI-Deficient Macrophages Protect Mice Against Metaflammation and Obesity-Induced Dysregulation of Glucose Homeostasis
title_short TACI-Deficient Macrophages Protect Mice Against Metaflammation and Obesity-Induced Dysregulation of Glucose Homeostasis
title_sort taci-deficient macrophages protect mice against metaflammation and obesity-induced dysregulation of glucose homeostasis
topic Immunology and Transplantation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054430/
https://www.ncbi.nlm.nih.gov/pubmed/29871859
http://dx.doi.org/10.2337/db17-1089
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