Cargando…
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...
Autores principales: | , , , , , , |
---|---|
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 |
_version_ | 1782179337304276992 |
---|---|
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. |
format | Text |
id | pubmed-2844826 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT luonanlan macrophageadiponectinexpressionimprovesinsulinsensitivityandprotectsagainstinflammationandatherosclerosis AT liujian macrophageadiponectinexpressionimprovesinsulinsensitivityandprotectsagainstinflammationandatherosclerosis AT chungbhong macrophageadiponectinexpressionimprovesinsulinsensitivityandprotectsagainstinflammationandatherosclerosis AT yangqinglin macrophageadiponectinexpressionimprovesinsulinsensitivityandprotectsagainstinflammationandatherosclerosis AT kleinrichardl macrophageadiponectinexpressionimprovesinsulinsensitivityandprotectsagainstinflammationandatherosclerosis AT garveywtimothy macrophageadiponectinexpressionimprovesinsulinsensitivityandprotectsagainstinflammationandatherosclerosis AT fuyuchang macrophageadiponectinexpressionimprovesinsulinsensitivityandprotectsagainstinflammationandatherosclerosis |