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Macrophage Adiponectin Expression Improves Insulin Sensitivity and Protects Against Inflammation and Atherosclerosis

OBJECTIVE: Adiponectin is one of several important metabolically active cytokines secreted from adipose tissue. Epidemiologic studies have associated low-circulating levels of this adipokine with multiple metabolic disorders including obesity, insulin resistance, type 2 diabetes, and cardiovascular...

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Autores principales: Luo, Nanlan, Liu, Jian, Chung, B. Hong, Yang, Qinglin, Klein, Richard L., Garvey, W. Timothy, Fu, Yuchang
Formato: Texto
Lenguaje:English
Publicado: American Diabetes Association 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2844826/
https://www.ncbi.nlm.nih.gov/pubmed/20350970
http://dx.doi.org/10.2337/db09-1338
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author Luo, Nanlan
Liu, Jian
Chung, B. Hong
Yang, Qinglin
Klein, Richard L.
Garvey, W. Timothy
Fu, Yuchang
author_facet Luo, Nanlan
Liu, Jian
Chung, B. Hong
Yang, Qinglin
Klein, Richard L.
Garvey, W. Timothy
Fu, Yuchang
author_sort Luo, Nanlan
collection PubMed
description OBJECTIVE: Adiponectin is one of several important metabolically active cytokines secreted from adipose tissue. Epidemiologic studies have associated low-circulating levels of this adipokine with multiple metabolic disorders including obesity, insulin resistance, type 2 diabetes, and cardiovascular disease. To investigate adiponectin-mediated changes in metabolism in vivo, we generated transgenic mice that specifically express the gene coding for human adiponectin in mouse macrophages using the human scavenger receptor A-I gene enhancer/promoter. METHODS AND RESULTS: Using this transgenic mouse model, we found that adiponectin expression was associated with reduced whole-animal body and fat-pad weight and an improved lipid accumulation in macrophages when these transgenic mice were fed with a high-fat diet. Moreover, these macrophage Ad-TG mice exhibit enhanced whole-body glucose tolerance and insulin sensitivity with reduced proinflammatory cytokines, MCP-1 and TNF-a (both in the serum and in the metabolic active macrophage), adipose tissue, and skeletal muscle under the high-fat diet condition. Additional studies demonstrated that these macrophage adiponectin transgenic animals exhibit reduced macrophage foam cell formation in the arterial wall when these transgenic mice were crossed with an LDL receptor–deficient mouse model and were fed a high-fat diet. CONCLUSIONS: These results suggest that adiponectin expressed in macrophages can physiologically modulate metabolic activities in vivo by improving metabolism in distal tissues. The use of macrophages as carriers for adiponectin, a molecule with antidiabetes, anti-inflammatory, and antiatherogenic properties, provides a novel and unique strategy for studying the mechanisms of adiponectin-mediated alterations in body metabolism in vivo.
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spelling pubmed-28448262011-04-01 Macrophage Adiponectin Expression Improves Insulin Sensitivity and Protects Against Inflammation and Atherosclerosis Luo, Nanlan Liu, Jian Chung, B. Hong Yang, Qinglin Klein, Richard L. Garvey, W. Timothy Fu, Yuchang Diabetes Original Article OBJECTIVE: Adiponectin is one of several important metabolically active cytokines secreted from adipose tissue. Epidemiologic studies have associated low-circulating levels of this adipokine with multiple metabolic disorders including obesity, insulin resistance, type 2 diabetes, and cardiovascular disease. To investigate adiponectin-mediated changes in metabolism in vivo, we generated transgenic mice that specifically express the gene coding for human adiponectin in mouse macrophages using the human scavenger receptor A-I gene enhancer/promoter. METHODS AND RESULTS: Using this transgenic mouse model, we found that adiponectin expression was associated with reduced whole-animal body and fat-pad weight and an improved lipid accumulation in macrophages when these transgenic mice were fed with a high-fat diet. Moreover, these macrophage Ad-TG mice exhibit enhanced whole-body glucose tolerance and insulin sensitivity with reduced proinflammatory cytokines, MCP-1 and TNF-a (both in the serum and in the metabolic active macrophage), adipose tissue, and skeletal muscle under the high-fat diet condition. Additional studies demonstrated that these macrophage adiponectin transgenic animals exhibit reduced macrophage foam cell formation in the arterial wall when these transgenic mice were crossed with an LDL receptor–deficient mouse model and were fed a high-fat diet. CONCLUSIONS: These results suggest that adiponectin expressed in macrophages can physiologically modulate metabolic activities in vivo by improving metabolism in distal tissues. The use of macrophages as carriers for adiponectin, a molecule with antidiabetes, anti-inflammatory, and antiatherogenic properties, provides a novel and unique strategy for studying the mechanisms of adiponectin-mediated alterations in body metabolism in vivo. American Diabetes Association 2010-04 /pmc/articles/PMC2844826/ /pubmed/20350970 http://dx.doi.org/10.2337/db09-1338 Text en © 2010 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. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Original Article
Luo, Nanlan
Liu, Jian
Chung, B. Hong
Yang, Qinglin
Klein, Richard L.
Garvey, W. Timothy
Fu, Yuchang
Macrophage Adiponectin Expression Improves Insulin Sensitivity and Protects Against Inflammation and Atherosclerosis
title Macrophage Adiponectin Expression Improves Insulin Sensitivity and Protects Against Inflammation and Atherosclerosis
title_full Macrophage Adiponectin Expression Improves Insulin Sensitivity and Protects Against Inflammation and Atherosclerosis
title_fullStr Macrophage Adiponectin Expression Improves Insulin Sensitivity and Protects Against Inflammation and Atherosclerosis
title_full_unstemmed Macrophage Adiponectin Expression Improves Insulin Sensitivity and Protects Against Inflammation and Atherosclerosis
title_short Macrophage Adiponectin Expression Improves Insulin Sensitivity and Protects Against Inflammation and Atherosclerosis
title_sort macrophage adiponectin expression improves insulin sensitivity and protects against inflammation and atherosclerosis
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2844826/
https://www.ncbi.nlm.nih.gov/pubmed/20350970
http://dx.doi.org/10.2337/db09-1338
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