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Involvement of Cbl-b-mediated macrophage inactivation in insulin resistance
Aging and overnutrition cause obesity in rodents and humans. It is well-known that obesity causes various diseases by producing insulin resistance (IR). Macrophages infiltrate the adipose tissue (AT) of obese individuals and cause chronic low-level inflammation associated with IR. Macrophage infiltr...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Baishideng Publishing Group Inc
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5348625/ https://www.ncbi.nlm.nih.gov/pubmed/28344752 http://dx.doi.org/10.4239/wjd.v8.i3.97 |
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author | Abe, Tomoki Hirasaka, Katsuya Nikawa, Takeshi |
author_facet | Abe, Tomoki Hirasaka, Katsuya Nikawa, Takeshi |
author_sort | Abe, Tomoki |
collection | PubMed |
description | Aging and overnutrition cause obesity in rodents and humans. It is well-known that obesity causes various diseases by producing insulin resistance (IR). Macrophages infiltrate the adipose tissue (AT) of obese individuals and cause chronic low-level inflammation associated with IR. Macrophage infiltration is regulated by the chemokines that are released from hypertrophied adipocytes and the immune cells in AT. Saturated fatty acids are recognized by toll-like receptor 4 (TLR4) and induce inflammatory responses in AT macrophages (ATMs). The inflammatory cytokines that are released from activated ATMs promote IR in peripheral organs, such as the liver, skeletal muscle and AT. Therefore, ATM activation is a therapeutic target for IR in obesity. The ubiquitin ligase Casitas b-lineage lymphoma-b (Cbl-b) appears to potently suppress macrophage migration and activation. Cbl-b is highly expressed in leukocytes and negatively regulates signals associated with migration and activation. Cbl-b deficiency enhances ATM accumulation and IR in aging- and diet-induced obese mice. Cbl-b inhibits migration-related signals and SFA-induced TLR4 signaling in ATMs. Thus, targeting Cbl-b may be a potential therapeutic strategy to reduce the IR induced by ATM activation. In this review, we summarize the regulatory functions of Cbl-b in ATMs. |
format | Online Article Text |
id | pubmed-5348625 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Baishideng Publishing Group Inc |
record_format | MEDLINE/PubMed |
spelling | pubmed-53486252017-03-25 Involvement of Cbl-b-mediated macrophage inactivation in insulin resistance Abe, Tomoki Hirasaka, Katsuya Nikawa, Takeshi World J Diabetes Minireviews Aging and overnutrition cause obesity in rodents and humans. It is well-known that obesity causes various diseases by producing insulin resistance (IR). Macrophages infiltrate the adipose tissue (AT) of obese individuals and cause chronic low-level inflammation associated with IR. Macrophage infiltration is regulated by the chemokines that are released from hypertrophied adipocytes and the immune cells in AT. Saturated fatty acids are recognized by toll-like receptor 4 (TLR4) and induce inflammatory responses in AT macrophages (ATMs). The inflammatory cytokines that are released from activated ATMs promote IR in peripheral organs, such as the liver, skeletal muscle and AT. Therefore, ATM activation is a therapeutic target for IR in obesity. The ubiquitin ligase Casitas b-lineage lymphoma-b (Cbl-b) appears to potently suppress macrophage migration and activation. Cbl-b is highly expressed in leukocytes and negatively regulates signals associated with migration and activation. Cbl-b deficiency enhances ATM accumulation and IR in aging- and diet-induced obese mice. Cbl-b inhibits migration-related signals and SFA-induced TLR4 signaling in ATMs. Thus, targeting Cbl-b may be a potential therapeutic strategy to reduce the IR induced by ATM activation. In this review, we summarize the regulatory functions of Cbl-b in ATMs. Baishideng Publishing Group Inc 2017-03-15 2017-03-15 /pmc/articles/PMC5348625/ /pubmed/28344752 http://dx.doi.org/10.4239/wjd.v8.i3.97 Text en ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved. http://creativecommons.org/licenses/by-nc/4.0/ This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. |
spellingShingle | Minireviews Abe, Tomoki Hirasaka, Katsuya Nikawa, Takeshi Involvement of Cbl-b-mediated macrophage inactivation in insulin resistance |
title | Involvement of Cbl-b-mediated macrophage inactivation in insulin resistance |
title_full | Involvement of Cbl-b-mediated macrophage inactivation in insulin resistance |
title_fullStr | Involvement of Cbl-b-mediated macrophage inactivation in insulin resistance |
title_full_unstemmed | Involvement of Cbl-b-mediated macrophage inactivation in insulin resistance |
title_short | Involvement of Cbl-b-mediated macrophage inactivation in insulin resistance |
title_sort | involvement of cbl-b-mediated macrophage inactivation in insulin resistance |
topic | Minireviews |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5348625/ https://www.ncbi.nlm.nih.gov/pubmed/28344752 http://dx.doi.org/10.4239/wjd.v8.i3.97 |
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