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Characterization of Distinct Subpopulations of Hepatic Macrophages in HFD/Obese Mice
The current dogma is that obesity-associated hepatic inflammation is due to increased Kupffer cell (KC) activation. However, recruited hepatic macrophages (RHMs) were recently shown to represent a sizable liver macrophage population in the context of obesity. Therefore, we assessed whether KCs and R...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375077/ https://www.ncbi.nlm.nih.gov/pubmed/25315009 http://dx.doi.org/10.2337/db14-1238 |
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author | Morinaga, Hidetaka Mayoral, Rafael Heinrichsdorff, Jan Osborn, Olivia Franck, Niclas Hah, Nasun Walenta, Evelyn Bandyopadhyay, Gautam Pessentheiner, Ariane R. Chi, Tyler J. Chung, Heekyung Bogner-Strauss, Juliane G. Evans, Ronald M. Olefsky, Jerrold M. Oh, Da Young |
author_facet | Morinaga, Hidetaka Mayoral, Rafael Heinrichsdorff, Jan Osborn, Olivia Franck, Niclas Hah, Nasun Walenta, Evelyn Bandyopadhyay, Gautam Pessentheiner, Ariane R. Chi, Tyler J. Chung, Heekyung Bogner-Strauss, Juliane G. Evans, Ronald M. Olefsky, Jerrold M. Oh, Da Young |
author_sort | Morinaga, Hidetaka |
collection | PubMed |
description | The current dogma is that obesity-associated hepatic inflammation is due to increased Kupffer cell (KC) activation. However, recruited hepatic macrophages (RHMs) were recently shown to represent a sizable liver macrophage population in the context of obesity. Therefore, we assessed whether KCs and RHMs, or both, represent the major liver inflammatory cell type in obesity. We used a combination of in vivo macrophage tracking methodologies and adoptive transfer techniques in which KCs and RHMs are differentially labeled with fluorescent markers. With these approaches, the inflammatory phenotype of these distinct macrophage populations was determined under lean and obese conditions. In vivo macrophage tracking revealed an approximately sixfold higher number of RHMs in obese mice than in lean mice, whereas the number of KCs was comparable. In addition, RHMs comprised smaller size and immature, monocyte-derived cells compared with KCs. Furthermore, RHMs from obese mice were more inflamed and expressed higher levels of tumor necrosis factor-α and interleukin-6 than RHMs from lean mice. A comparison of the MCP-1/C-C chemokine receptor type 2 (CCR2) chemokine system between the two cell types showed that the ligand (MCP-1) is more highly expressed in KCs than in RHMs, whereas CCR2 expression is approximately fivefold greater in RHMs. We conclude that KCs can participate in obesity-induced inflammation by causing the recruitment of RHMs, which are distinct from KCs and are not precursors to KCs. These RHMs then enhance the severity of obesity-induced inflammation and hepatic insulin resistance. |
format | Online Article Text |
id | pubmed-4375077 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-43750772016-04-01 Characterization of Distinct Subpopulations of Hepatic Macrophages in HFD/Obese Mice Morinaga, Hidetaka Mayoral, Rafael Heinrichsdorff, Jan Osborn, Olivia Franck, Niclas Hah, Nasun Walenta, Evelyn Bandyopadhyay, Gautam Pessentheiner, Ariane R. Chi, Tyler J. Chung, Heekyung Bogner-Strauss, Juliane G. Evans, Ronald M. Olefsky, Jerrold M. Oh, Da Young Diabetes Metabolism The current dogma is that obesity-associated hepatic inflammation is due to increased Kupffer cell (KC) activation. However, recruited hepatic macrophages (RHMs) were recently shown to represent a sizable liver macrophage population in the context of obesity. Therefore, we assessed whether KCs and RHMs, or both, represent the major liver inflammatory cell type in obesity. We used a combination of in vivo macrophage tracking methodologies and adoptive transfer techniques in which KCs and RHMs are differentially labeled with fluorescent markers. With these approaches, the inflammatory phenotype of these distinct macrophage populations was determined under lean and obese conditions. In vivo macrophage tracking revealed an approximately sixfold higher number of RHMs in obese mice than in lean mice, whereas the number of KCs was comparable. In addition, RHMs comprised smaller size and immature, monocyte-derived cells compared with KCs. Furthermore, RHMs from obese mice were more inflamed and expressed higher levels of tumor necrosis factor-α and interleukin-6 than RHMs from lean mice. A comparison of the MCP-1/C-C chemokine receptor type 2 (CCR2) chemokine system between the two cell types showed that the ligand (MCP-1) is more highly expressed in KCs than in RHMs, whereas CCR2 expression is approximately fivefold greater in RHMs. We conclude that KCs can participate in obesity-induced inflammation by causing the recruitment of RHMs, which are distinct from KCs and are not precursors to KCs. These RHMs then enhance the severity of obesity-induced inflammation and hepatic insulin resistance. American Diabetes Association 2015-04 2014-10-14 /pmc/articles/PMC4375077/ /pubmed/25315009 http://dx.doi.org/10.2337/db14-1238 Text en © 2015 by the American Diabetes Association. Readers 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. |
spellingShingle | Metabolism Morinaga, Hidetaka Mayoral, Rafael Heinrichsdorff, Jan Osborn, Olivia Franck, Niclas Hah, Nasun Walenta, Evelyn Bandyopadhyay, Gautam Pessentheiner, Ariane R. Chi, Tyler J. Chung, Heekyung Bogner-Strauss, Juliane G. Evans, Ronald M. Olefsky, Jerrold M. Oh, Da Young Characterization of Distinct Subpopulations of Hepatic Macrophages in HFD/Obese Mice |
title | Characterization of Distinct Subpopulations of Hepatic Macrophages in HFD/Obese Mice |
title_full | Characterization of Distinct Subpopulations of Hepatic Macrophages in HFD/Obese Mice |
title_fullStr | Characterization of Distinct Subpopulations of Hepatic Macrophages in HFD/Obese Mice |
title_full_unstemmed | Characterization of Distinct Subpopulations of Hepatic Macrophages in HFD/Obese Mice |
title_short | Characterization of Distinct Subpopulations of Hepatic Macrophages in HFD/Obese Mice |
title_sort | characterization of distinct subpopulations of hepatic macrophages in hfd/obese mice |
topic | Metabolism |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375077/ https://www.ncbi.nlm.nih.gov/pubmed/25315009 http://dx.doi.org/10.2337/db14-1238 |
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