Adipose tissue macrophages induce hepatic neutrophil recruitment and macrophage accumulation in mice

Publication Date:
2018-06-08
Publisher:
BMJ Publishing Group
Print ISSN:
0017-5749
Electronic ISSN:
1468-3288
Topics:
Medicine
Keywords:
Gut
Published by:
http://www.bmj.com/
_version_ 1836398964184711169
autor Bijnen, M., Josefs, T., Cuijpers, I., Maalsen, C. J., van de Gaar, J., Vroomen, M., Wijnands, E., Rensen, S. S., Greve, J. W. M., Hofker, M. H., Biessen, E. A. L., Stehouwer, C. D. A., Schalkwijk, C. G., Wouters, K.
beschreibung Objective Obesity is a risk factor for non-alcoholic steatohepatitis (NASH). This risk has been attributed to visceral adipose tissue (vAT) expansion associated with increased proinflammatory mediators. Accumulation of CD11c + proinflammatory adipose tissue macrophages (ATM) is an important driver of vAT inflammation. We investigated the role of ATMs in hepatic inflammation during NASH development. Design vAT isolated from lean, obese or ATM-depleted (using clodronate liposomes) obese mice was transplanted to lean ldlr -/- acceptor mice. Systemic and hepatic inflammation was assessed either after 2 weeks on standard chow or after 8 weeks on high cholesterol diet (HCD) to induce NASH. Results Transplanting donor vAT from obese mice increased HCD-induced hepatic macrophage content compared with lean-transplanted mice, worsening liver damage. ATM depletion prior to vAT transplantation reduced this increased hepatic macrophage accumulation. On chow, vAT transplantation induced a more pronounced increase in circulating and hepatic neutrophil numbers in obese-transplanted than lean-transplanted mice, while ATM depletion prior to vAT transplantation reversed this effect. Microarray analysis of fluorescence-activated cell sorting of CD11c + and CD11c – macrophages isolated from donor adipose tissue showed that obesity resulted in enhanced expression of neutrophil chemotaxis genes specifically in CD11c + ATMs. Involvement of the neutrophil chemotaxis proteins, CXCL14 and CXCL16, was confirmed by culturing vAT. In humans, CD11c expression in vAT of obese individuals correlated with vAT expression of neutrophil chemotactic genes and with hepatic expression of neutrophil and macrophage marker genes. Conclusion ATMs from obese vAT induce hepatic macrophage accumulation during NASH development, possibly by enhancing neutrophil recruitment.
citation_standardnr 6278851
datenlieferant ipn_articles
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feed_publisher BMJ Publishing Group
feed_publisher_url http://www.bmj.com/
insertion_date 2018-06-08
journaleissn 1468-3288
journalissn 0017-5749
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher BMJ Publishing Group
quelle Gut
relation http://gut.bmj.com/cgi/content/short/67/7/1317?rss=1
schlagwort Gut
search_space articles
shingle_author_1 Bijnen, M., Josefs, T., Cuijpers, I., Maalsen, C. J., van de Gaar, J., Vroomen, M., Wijnands, E., Rensen, S. S., Greve, J. W. M., Hofker, M. H., Biessen, E. A. L., Stehouwer, C. D. A., Schalkwijk, C. G., Wouters, K.
shingle_author_2 Bijnen, M., Josefs, T., Cuijpers, I., Maalsen, C. J., van de Gaar, J., Vroomen, M., Wijnands, E., Rensen, S. S., Greve, J. W. M., Hofker, M. H., Biessen, E. A. L., Stehouwer, C. D. A., Schalkwijk, C. G., Wouters, K.
shingle_author_3 Bijnen, M., Josefs, T., Cuijpers, I., Maalsen, C. J., van de Gaar, J., Vroomen, M., Wijnands, E., Rensen, S. S., Greve, J. W. M., Hofker, M. H., Biessen, E. A. L., Stehouwer, C. D. A., Schalkwijk, C. G., Wouters, K.
shingle_author_4 Bijnen, M., Josefs, T., Cuijpers, I., Maalsen, C. J., van de Gaar, J., Vroomen, M., Wijnands, E., Rensen, S. S., Greve, J. W. M., Hofker, M. H., Biessen, E. A. L., Stehouwer, C. D. A., Schalkwijk, C. G., Wouters, K.
shingle_catch_all_1 Adipose tissue macrophages induce hepatic neutrophil recruitment and macrophage accumulation in mice
Gut
Objective Obesity is a risk factor for non-alcoholic steatohepatitis (NASH). This risk has been attributed to visceral adipose tissue (vAT) expansion associated with increased proinflammatory mediators. Accumulation of CD11c + proinflammatory adipose tissue macrophages (ATM) is an important driver of vAT inflammation. We investigated the role of ATMs in hepatic inflammation during NASH development. Design vAT isolated from lean, obese or ATM-depleted (using clodronate liposomes) obese mice was transplanted to lean ldlr -/- acceptor mice. Systemic and hepatic inflammation was assessed either after 2 weeks on standard chow or after 8 weeks on high cholesterol diet (HCD) to induce NASH. Results Transplanting donor vAT from obese mice increased HCD-induced hepatic macrophage content compared with lean-transplanted mice, worsening liver damage. ATM depletion prior to vAT transplantation reduced this increased hepatic macrophage accumulation. On chow, vAT transplantation induced a more pronounced increase in circulating and hepatic neutrophil numbers in obese-transplanted than lean-transplanted mice, while ATM depletion prior to vAT transplantation reversed this effect. Microarray analysis of fluorescence-activated cell sorting of CD11c + and CD11c – macrophages isolated from donor adipose tissue showed that obesity resulted in enhanced expression of neutrophil chemotaxis genes specifically in CD11c + ATMs. Involvement of the neutrophil chemotaxis proteins, CXCL14 and CXCL16, was confirmed by culturing vAT. In humans, CD11c expression in vAT of obese individuals correlated with vAT expression of neutrophil chemotactic genes and with hepatic expression of neutrophil and macrophage marker genes. Conclusion ATMs from obese vAT induce hepatic macrophage accumulation during NASH development, possibly by enhancing neutrophil recruitment.
Bijnen, M., Josefs, T., Cuijpers, I., Maalsen, C. J., van de Gaar, J., Vroomen, M., Wijnands, E., Rensen, S. S., Greve, J. W. M., Hofker, M. H., Biessen, E. A. L., Stehouwer, C. D. A., Schalkwijk, C. G., Wouters, K.
BMJ Publishing Group
0017-5749
00175749
1468-3288
14683288
shingle_catch_all_2 Adipose tissue macrophages induce hepatic neutrophil recruitment and macrophage accumulation in mice
Gut
Objective Obesity is a risk factor for non-alcoholic steatohepatitis (NASH). This risk has been attributed to visceral adipose tissue (vAT) expansion associated with increased proinflammatory mediators. Accumulation of CD11c + proinflammatory adipose tissue macrophages (ATM) is an important driver of vAT inflammation. We investigated the role of ATMs in hepatic inflammation during NASH development. Design vAT isolated from lean, obese or ATM-depleted (using clodronate liposomes) obese mice was transplanted to lean ldlr -/- acceptor mice. Systemic and hepatic inflammation was assessed either after 2 weeks on standard chow or after 8 weeks on high cholesterol diet (HCD) to induce NASH. Results Transplanting donor vAT from obese mice increased HCD-induced hepatic macrophage content compared with lean-transplanted mice, worsening liver damage. ATM depletion prior to vAT transplantation reduced this increased hepatic macrophage accumulation. On chow, vAT transplantation induced a more pronounced increase in circulating and hepatic neutrophil numbers in obese-transplanted than lean-transplanted mice, while ATM depletion prior to vAT transplantation reversed this effect. Microarray analysis of fluorescence-activated cell sorting of CD11c + and CD11c – macrophages isolated from donor adipose tissue showed that obesity resulted in enhanced expression of neutrophil chemotaxis genes specifically in CD11c + ATMs. Involvement of the neutrophil chemotaxis proteins, CXCL14 and CXCL16, was confirmed by culturing vAT. In humans, CD11c expression in vAT of obese individuals correlated with vAT expression of neutrophil chemotactic genes and with hepatic expression of neutrophil and macrophage marker genes. Conclusion ATMs from obese vAT induce hepatic macrophage accumulation during NASH development, possibly by enhancing neutrophil recruitment.
Bijnen, M., Josefs, T., Cuijpers, I., Maalsen, C. J., van de Gaar, J., Vroomen, M., Wijnands, E., Rensen, S. S., Greve, J. W. M., Hofker, M. H., Biessen, E. A. L., Stehouwer, C. D. A., Schalkwijk, C. G., Wouters, K.
BMJ Publishing Group
0017-5749
00175749
1468-3288
14683288
shingle_catch_all_3 Adipose tissue macrophages induce hepatic neutrophil recruitment and macrophage accumulation in mice
Gut
Objective Obesity is a risk factor for non-alcoholic steatohepatitis (NASH). This risk has been attributed to visceral adipose tissue (vAT) expansion associated with increased proinflammatory mediators. Accumulation of CD11c + proinflammatory adipose tissue macrophages (ATM) is an important driver of vAT inflammation. We investigated the role of ATMs in hepatic inflammation during NASH development. Design vAT isolated from lean, obese or ATM-depleted (using clodronate liposomes) obese mice was transplanted to lean ldlr -/- acceptor mice. Systemic and hepatic inflammation was assessed either after 2 weeks on standard chow or after 8 weeks on high cholesterol diet (HCD) to induce NASH. Results Transplanting donor vAT from obese mice increased HCD-induced hepatic macrophage content compared with lean-transplanted mice, worsening liver damage. ATM depletion prior to vAT transplantation reduced this increased hepatic macrophage accumulation. On chow, vAT transplantation induced a more pronounced increase in circulating and hepatic neutrophil numbers in obese-transplanted than lean-transplanted mice, while ATM depletion prior to vAT transplantation reversed this effect. Microarray analysis of fluorescence-activated cell sorting of CD11c + and CD11c – macrophages isolated from donor adipose tissue showed that obesity resulted in enhanced expression of neutrophil chemotaxis genes specifically in CD11c + ATMs. Involvement of the neutrophil chemotaxis proteins, CXCL14 and CXCL16, was confirmed by culturing vAT. In humans, CD11c expression in vAT of obese individuals correlated with vAT expression of neutrophil chemotactic genes and with hepatic expression of neutrophil and macrophage marker genes. Conclusion ATMs from obese vAT induce hepatic macrophage accumulation during NASH development, possibly by enhancing neutrophil recruitment.
Bijnen, M., Josefs, T., Cuijpers, I., Maalsen, C. J., van de Gaar, J., Vroomen, M., Wijnands, E., Rensen, S. S., Greve, J. W. M., Hofker, M. H., Biessen, E. A. L., Stehouwer, C. D. A., Schalkwijk, C. G., Wouters, K.
BMJ Publishing Group
0017-5749
00175749
1468-3288
14683288
shingle_catch_all_4 Adipose tissue macrophages induce hepatic neutrophil recruitment and macrophage accumulation in mice
Gut
Objective Obesity is a risk factor for non-alcoholic steatohepatitis (NASH). This risk has been attributed to visceral adipose tissue (vAT) expansion associated with increased proinflammatory mediators. Accumulation of CD11c + proinflammatory adipose tissue macrophages (ATM) is an important driver of vAT inflammation. We investigated the role of ATMs in hepatic inflammation during NASH development. Design vAT isolated from lean, obese or ATM-depleted (using clodronate liposomes) obese mice was transplanted to lean ldlr -/- acceptor mice. Systemic and hepatic inflammation was assessed either after 2 weeks on standard chow or after 8 weeks on high cholesterol diet (HCD) to induce NASH. Results Transplanting donor vAT from obese mice increased HCD-induced hepatic macrophage content compared with lean-transplanted mice, worsening liver damage. ATM depletion prior to vAT transplantation reduced this increased hepatic macrophage accumulation. On chow, vAT transplantation induced a more pronounced increase in circulating and hepatic neutrophil numbers in obese-transplanted than lean-transplanted mice, while ATM depletion prior to vAT transplantation reversed this effect. Microarray analysis of fluorescence-activated cell sorting of CD11c + and CD11c – macrophages isolated from donor adipose tissue showed that obesity resulted in enhanced expression of neutrophil chemotaxis genes specifically in CD11c + ATMs. Involvement of the neutrophil chemotaxis proteins, CXCL14 and CXCL16, was confirmed by culturing vAT. In humans, CD11c expression in vAT of obese individuals correlated with vAT expression of neutrophil chemotactic genes and with hepatic expression of neutrophil and macrophage marker genes. Conclusion ATMs from obese vAT induce hepatic macrophage accumulation during NASH development, possibly by enhancing neutrophil recruitment.
Bijnen, M., Josefs, T., Cuijpers, I., Maalsen, C. J., van de Gaar, J., Vroomen, M., Wijnands, E., Rensen, S. S., Greve, J. W. M., Hofker, M. H., Biessen, E. A. L., Stehouwer, C. D. A., Schalkwijk, C. G., Wouters, K.
BMJ Publishing Group
0017-5749
00175749
1468-3288
14683288
shingle_title_1 Adipose tissue macrophages induce hepatic neutrophil recruitment and macrophage accumulation in mice
shingle_title_2 Adipose tissue macrophages induce hepatic neutrophil recruitment and macrophage accumulation in mice
shingle_title_3 Adipose tissue macrophages induce hepatic neutrophil recruitment and macrophage accumulation in mice
shingle_title_4 Adipose tissue macrophages induce hepatic neutrophil recruitment and macrophage accumulation in mice
timestamp 2025-06-30T23:35:26.683Z
titel Adipose tissue macrophages induce hepatic neutrophil recruitment and macrophage accumulation in mice
titel_suche Adipose tissue macrophages induce hepatic neutrophil recruitment and macrophage accumulation in mice
topic WW-YZ
uid ipn_articles_6278851