Cargando…
An accelerated mouse model for atherosclerosis and adipose tissue inflammation
BACKGROUND: Obesity and particularly the metabolic syndrome, which is often associated with obesity, combine a major risk for type 2 diabetes and cardiovascular disease. Emerging evidence indicate obesity-associated subclinical inflammation primarily originating from adipose tissue as a common cause...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3902066/ https://www.ncbi.nlm.nih.gov/pubmed/24438079 http://dx.doi.org/10.1186/1475-2840-13-23 |
_version_ | 1782300944716791808 |
---|---|
author | Neuhofer, Angelika Wernly, Bernhard Leitner, Lukas Sarabi, Alisina Sommer, Nicole G Staffler, Günther Zeyda, Maximilian Stulnig, Thomas M |
author_facet | Neuhofer, Angelika Wernly, Bernhard Leitner, Lukas Sarabi, Alisina Sommer, Nicole G Staffler, Günther Zeyda, Maximilian Stulnig, Thomas M |
author_sort | Neuhofer, Angelika |
collection | PubMed |
description | BACKGROUND: Obesity and particularly the metabolic syndrome, which is often associated with obesity, combine a major risk for type 2 diabetes and cardiovascular disease. Emerging evidence indicate obesity-associated subclinical inflammation primarily originating from adipose tissue as a common cause for type 2 diabetes and cardiovascular disease. However, a suitable and well-characterized mouse model to simultaneously study obesity-associated metabolic disorders and atherosclerosis is not available yet. Here we established and characterized a murine model combining diet-induced obesity and associated adipose tissue inflammation and metabolic deteriorations as well as atherosclerosis, hence reflecting the human situation of cardio-metabolic disease. METHODS: We compared a common high-fat diet with 0.15% cholesterol (HFC), and a high-fat, high-sucrose diet with 0.15% cholesterol (HFSC) fed to LDL receptor-deficient (LDLR(-/-)) mice. Insulin resistance, glucose tolerance, atherosclerotic lesion formation, hepatic lipid accumulation, and inflammatory gene expression in adipose tissue and liver were assessed. RESULTS: After 12–16 weeks, LDLR(-/-) mice fed HFSC or HFC developed significant diet-induced obesity, adipose tissue inflammation, insulin resistance, and impaired glucose tolerance compared to lean controls. Notably, HFSC-fed mice developed significantly higher adipose tissue inflammation in parallel with significantly elevated atherosclerotic lesion area compared to those on HFC. Moreover, LDLR(-/-) mice on HFSC showed increased insulin resistance and impaired glucose tolerance relative to those on HFC. After prolonged feeding (20 weeks), however, no significant differences in inflammatory and metabolic parameters as well as atherosclerotic lesion formation were detectable any more between LDLR(-/-) mice fed HFSC or HFC. CONCLUSION: The use of high sucrose rather than more complex carbohydrates in high-fat diets significantly accelerates development of obesity-driven metabolic complications and atherosclerotic plaque formation parallel to obesity-induced adipose tissue inflammation in LDLR(-/-) mice. Hence LDLR(-/-) mice fed high-fat high-sucrose cholesterol-enriched diet appear to be a suitable and time-saving animal model for cardio-metabolic disease. Moreover our results support the suggested interrelation between adipose tissue inflammation and atherosclerotic plaque formation. |
format | Online Article Text |
id | pubmed-3902066 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-39020662014-01-26 An accelerated mouse model for atherosclerosis and adipose tissue inflammation Neuhofer, Angelika Wernly, Bernhard Leitner, Lukas Sarabi, Alisina Sommer, Nicole G Staffler, Günther Zeyda, Maximilian Stulnig, Thomas M Cardiovasc Diabetol Methodology BACKGROUND: Obesity and particularly the metabolic syndrome, which is often associated with obesity, combine a major risk for type 2 diabetes and cardiovascular disease. Emerging evidence indicate obesity-associated subclinical inflammation primarily originating from adipose tissue as a common cause for type 2 diabetes and cardiovascular disease. However, a suitable and well-characterized mouse model to simultaneously study obesity-associated metabolic disorders and atherosclerosis is not available yet. Here we established and characterized a murine model combining diet-induced obesity and associated adipose tissue inflammation and metabolic deteriorations as well as atherosclerosis, hence reflecting the human situation of cardio-metabolic disease. METHODS: We compared a common high-fat diet with 0.15% cholesterol (HFC), and a high-fat, high-sucrose diet with 0.15% cholesterol (HFSC) fed to LDL receptor-deficient (LDLR(-/-)) mice. Insulin resistance, glucose tolerance, atherosclerotic lesion formation, hepatic lipid accumulation, and inflammatory gene expression in adipose tissue and liver were assessed. RESULTS: After 12–16 weeks, LDLR(-/-) mice fed HFSC or HFC developed significant diet-induced obesity, adipose tissue inflammation, insulin resistance, and impaired glucose tolerance compared to lean controls. Notably, HFSC-fed mice developed significantly higher adipose tissue inflammation in parallel with significantly elevated atherosclerotic lesion area compared to those on HFC. Moreover, LDLR(-/-) mice on HFSC showed increased insulin resistance and impaired glucose tolerance relative to those on HFC. After prolonged feeding (20 weeks), however, no significant differences in inflammatory and metabolic parameters as well as atherosclerotic lesion formation were detectable any more between LDLR(-/-) mice fed HFSC or HFC. CONCLUSION: The use of high sucrose rather than more complex carbohydrates in high-fat diets significantly accelerates development of obesity-driven metabolic complications and atherosclerotic plaque formation parallel to obesity-induced adipose tissue inflammation in LDLR(-/-) mice. Hence LDLR(-/-) mice fed high-fat high-sucrose cholesterol-enriched diet appear to be a suitable and time-saving animal model for cardio-metabolic disease. Moreover our results support the suggested interrelation between adipose tissue inflammation and atherosclerotic plaque formation. BioMed Central 2014-01-17 /pmc/articles/PMC3902066/ /pubmed/24438079 http://dx.doi.org/10.1186/1475-2840-13-23 Text en Copyright © 2014 Neuhofer et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Methodology Neuhofer, Angelika Wernly, Bernhard Leitner, Lukas Sarabi, Alisina Sommer, Nicole G Staffler, Günther Zeyda, Maximilian Stulnig, Thomas M An accelerated mouse model for atherosclerosis and adipose tissue inflammation |
title | An accelerated mouse model for atherosclerosis and adipose tissue inflammation |
title_full | An accelerated mouse model for atherosclerosis and adipose tissue inflammation |
title_fullStr | An accelerated mouse model for atherosclerosis and adipose tissue inflammation |
title_full_unstemmed | An accelerated mouse model for atherosclerosis and adipose tissue inflammation |
title_short | An accelerated mouse model for atherosclerosis and adipose tissue inflammation |
title_sort | accelerated mouse model for atherosclerosis and adipose tissue inflammation |
topic | Methodology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3902066/ https://www.ncbi.nlm.nih.gov/pubmed/24438079 http://dx.doi.org/10.1186/1475-2840-13-23 |
work_keys_str_mv | AT neuhoferangelika anacceleratedmousemodelforatherosclerosisandadiposetissueinflammation AT wernlybernhard anacceleratedmousemodelforatherosclerosisandadiposetissueinflammation AT leitnerlukas anacceleratedmousemodelforatherosclerosisandadiposetissueinflammation AT sarabialisina anacceleratedmousemodelforatherosclerosisandadiposetissueinflammation AT sommernicoleg anacceleratedmousemodelforatherosclerosisandadiposetissueinflammation AT stafflergunther anacceleratedmousemodelforatherosclerosisandadiposetissueinflammation AT zeydamaximilian anacceleratedmousemodelforatherosclerosisandadiposetissueinflammation AT stulnigthomasm anacceleratedmousemodelforatherosclerosisandadiposetissueinflammation AT neuhoferangelika acceleratedmousemodelforatherosclerosisandadiposetissueinflammation AT wernlybernhard acceleratedmousemodelforatherosclerosisandadiposetissueinflammation AT leitnerlukas acceleratedmousemodelforatherosclerosisandadiposetissueinflammation AT sarabialisina acceleratedmousemodelforatherosclerosisandadiposetissueinflammation AT sommernicoleg acceleratedmousemodelforatherosclerosisandadiposetissueinflammation AT stafflergunther acceleratedmousemodelforatherosclerosisandadiposetissueinflammation AT zeydamaximilian acceleratedmousemodelforatherosclerosisandadiposetissueinflammation AT stulnigthomasm acceleratedmousemodelforatherosclerosisandadiposetissueinflammation |