Obesity increases inflammation and impairs lymphatic function in a mouse model of lymphedema
Identifieur interne : 006687 ( Ncbi/Curation ); précédent : 006686; suivant : 006688Obesity increases inflammation and impairs lymphatic function in a mouse model of lymphedema
Auteurs : Ira L. Savetsky ; Jeremy S. Torrisi ; Daniel A. Cuzzone ; Swapna Ghanta ; Nicholas J. Albano ; Jason C. Gardenier ; Walter J. Joseph ; Babak J. MehraraSource :
- American Journal of Physiology - Heart and Circulatory Physiology [ 0363-6135 ] ; 2014.
Descripteurs français
- KwdFr :
- Adiposité, Alimentation riche en graisse, Animaux, Facteurs temps, Fibrose, Graisse sous-cutanée (physiopathologie), Granulocytes neutrophiles (immunologie), Huile de croton, Indice de gravité médicale, Infiltration par les neutrophiles, Inflammation (), Inflammation (immunologie), Inflammation (physiopathologie), Inflammation (étiologie), Lymphoedème (anatomopathologie), Lymphoedème (immunologie), Lymphoedème (physiopathologie), Lymphoedème (étiologie), Macrophages (immunologie), Modèles animaux de maladie humaine, Mâle, Obésité (), Obésité (immunologie), Obésité (physiopathologie), Phénotype, Souris, Souris de lignée C57BL, Système lymphatique (anatomopathologie), Système lymphatique (immunologie), Système lymphatique (physiopathologie).
- MESH :
- anatomopathologie : Lymphoedème, Système lymphatique.
- immunologie : Granulocytes neutrophiles, Inflammation, Lymphoedème, Macrophages, Obésité, Système lymphatique.
- physiopathologie : Graisse sous-cutanée, Inflammation, Lymphoedème, Obésité, Système lymphatique.
- étiologie : Inflammation, Lymphoedème.
- Adiposité, Alimentation riche en graisse, Animaux, Facteurs temps, Fibrose, Huile de croton, Indice de gravité médicale, Infiltration par les neutrophiles, Inflammation, Modèles animaux de maladie humaine, Mâle, Obésité, Phénotype, Souris, Souris de lignée C57BL.
English descriptors
- KwdEn :
- Adiposity, Animals, Croton Oil, Diet, High-Fat, Disease Models, Animal, Fibrosis, Inflammation (chemically induced), Inflammation (etiology), Inflammation (immunology), Inflammation (physiopathology), Lymphatic System (immunology), Lymphatic System (pathology), Lymphatic System (physiopathology), Lymphedema (etiology), Lymphedema (immunology), Lymphedema (pathology), Lymphedema (physiopathology), Macrophages (immunology), Male, Mice, Mice, Inbred C57BL, Neutrophil Infiltration, Neutrophils (immunology), Obesity (complications), Obesity (immunology), Obesity (physiopathology), Phenotype, Severity of Illness Index, Subcutaneous Fat (physiopathology), Time Factors.
- MESH :
- chemical : Croton Oil.
- chemically induced : Inflammation.
- complications : Obesity.
- etiology : Inflammation, Lymphedema.
- immunology : Inflammation, Lymphatic System, Lymphedema, Macrophages, Neutrophils, Obesity.
- pathology : Lymphatic System, Lymphedema.
- physiopathology : Inflammation, Lymphatic System, Lymphedema, Obesity, Subcutaneous Fat.
- Adiposity, Animals, Diet, High-Fat, Disease Models, Animal, Fibrosis, Male, Mice, Mice, Inbred C57BL, Neutrophil Infiltration, Phenotype, Severity of Illness Index, Time Factors.
Abstract
Although obesity is a major clinical risk factor for lymphedema, the mechanisms that regulate this effect remain unknown. Recent reports have demonstrated that obesity is associated with acquired lymphatic dysfunction. The purpose of this study was to determine how obesity-induced lymphatic dysfunction modulates the pathological effects of lymphatic injury in a mouse model. We used a diet-induced model of obesity in adult male C57BL/6J mice in which experimental animals were fed a high-fat diet and control animals were fed a normal chow diet for 8–10 wk. We then surgically ablated the superficial and deep lymphatics of the midportion of the tail. Six weeks postoperatively, we analyzed changes in lymphatic function, adipose deposition, inflammation, and fibrosis. We also compared responses to acute inflammatory stimuli in obese and lean mice. Compared with lean control mice, obese mice had baseline decreased lymphatic function. Lymphedema in obese mice further impaired lymphatic function and resulted in increased subcutaneous adipose deposition, increased CD45+ and CD4+ cell inflammation (
Url:
DOI: 10.1152/ajpheart.00244.2014
PubMed: 24858842
PubMed Central: 4101643
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PMC:4101643Le document en format XML
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adiposity</term>
<term>Animals</term>
<term>Croton Oil</term>
<term>Diet, High-Fat</term>
<term>Disease Models, Animal</term>
<term>Fibrosis</term>
<term>Inflammation (chemically induced)</term>
<term>Inflammation (etiology)</term>
<term>Inflammation (immunology)</term>
<term>Inflammation (physiopathology)</term>
<term>Lymphatic System (immunology)</term>
<term>Lymphatic System (pathology)</term>
<term>Lymphatic System (physiopathology)</term>
<term>Lymphedema (etiology)</term>
<term>Lymphedema (immunology)</term>
<term>Lymphedema (pathology)</term>
<term>Lymphedema (physiopathology)</term>
<term>Macrophages (immunology)</term>
<term>Male</term>
<term>Mice</term>
<term>Mice, Inbred C57BL</term>
<term>Neutrophil Infiltration</term>
<term>Neutrophils (immunology)</term>
<term>Obesity (complications)</term>
<term>Obesity (immunology)</term>
<term>Obesity (physiopathology)</term>
<term>Phenotype</term>
<term>Severity of Illness Index</term>
<term>Subcutaneous Fat (physiopathology)</term>
<term>Time Factors</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Adiposité</term>
<term>Alimentation riche en graisse</term>
<term>Animaux</term>
<term>Facteurs temps</term>
<term>Fibrose</term>
<term>Graisse sous-cutanée (physiopathologie)</term>
<term>Granulocytes neutrophiles (immunologie)</term>
<term>Huile de croton</term>
<term>Indice de gravité médicale</term>
<term>Infiltration par les neutrophiles</term>
<term>Inflammation ()</term>
<term>Inflammation (immunologie)</term>
<term>Inflammation (physiopathologie)</term>
<term>Inflammation (étiologie)</term>
<term>Lymphoedème (anatomopathologie)</term>
<term>Lymphoedème (immunologie)</term>
<term>Lymphoedème (physiopathologie)</term>
<term>Lymphoedème (étiologie)</term>
<term>Macrophages (immunologie)</term>
<term>Modèles animaux de maladie humaine</term>
<term>Mâle</term>
<term>Obésité ()</term>
<term>Obésité (immunologie)</term>
<term>Obésité (physiopathologie)</term>
<term>Phénotype</term>
<term>Souris</term>
<term>Souris de lignée C57BL</term>
<term>Système lymphatique (anatomopathologie)</term>
<term>Système lymphatique (immunologie)</term>
<term>Système lymphatique (physiopathologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" xml:lang="en"><term>Croton Oil</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Lymphoedème</term>
<term>Système lymphatique</term>
</keywords>
<keywords scheme="MESH" qualifier="chemically induced" xml:lang="en"><term>Inflammation</term>
</keywords>
<keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Obesity</term>
</keywords>
<keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Inflammation</term>
<term>Lymphedema</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Granulocytes neutrophiles</term>
<term>Inflammation</term>
<term>Lymphoedème</term>
<term>Macrophages</term>
<term>Obésité</term>
<term>Système lymphatique</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Inflammation</term>
<term>Lymphatic System</term>
<term>Lymphedema</term>
<term>Macrophages</term>
<term>Neutrophils</term>
<term>Obesity</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Lymphatic System</term>
<term>Lymphedema</term>
</keywords>
<keywords scheme="MESH" qualifier="physiopathologie" xml:lang="fr"><term>Graisse sous-cutanée</term>
<term>Inflammation</term>
<term>Lymphoedème</term>
<term>Obésité</term>
<term>Système lymphatique</term>
</keywords>
<keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Inflammation</term>
<term>Lymphatic System</term>
<term>Lymphedema</term>
<term>Obesity</term>
<term>Subcutaneous Fat</term>
</keywords>
<keywords scheme="MESH" qualifier="étiologie" xml:lang="fr"><term>Inflammation</term>
<term>Lymphoedème</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adiposity</term>
<term>Animals</term>
<term>Diet, High-Fat</term>
<term>Disease Models, Animal</term>
<term>Fibrosis</term>
<term>Male</term>
<term>Mice</term>
<term>Mice, Inbred C57BL</term>
<term>Neutrophil Infiltration</term>
<term>Phenotype</term>
<term>Severity of Illness Index</term>
<term>Time Factors</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Adiposité</term>
<term>Alimentation riche en graisse</term>
<term>Animaux</term>
<term>Facteurs temps</term>
<term>Fibrose</term>
<term>Huile de croton</term>
<term>Indice de gravité médicale</term>
<term>Infiltration par les neutrophiles</term>
<term>Inflammation</term>
<term>Modèles animaux de maladie humaine</term>
<term>Mâle</term>
<term>Obésité</term>
<term>Phénotype</term>
<term>Souris</term>
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<front><div type="abstract" xml:lang="en"><p>Although obesity is a major clinical risk factor for lymphedema, the mechanisms that regulate this effect remain unknown. Recent reports have demonstrated that obesity is associated with acquired lymphatic dysfunction. The purpose of this study was to determine how obesity-induced lymphatic dysfunction modulates the pathological effects of lymphatic injury in a mouse model. We used a diet-induced model of obesity in adult male C57BL/6J mice in which experimental animals were fed a high-fat diet and control animals were fed a normal chow diet for 8–10 wk. We then surgically ablated the superficial and deep lymphatics of the midportion of the tail. Six weeks postoperatively, we analyzed changes in lymphatic function, adipose deposition, inflammation, and fibrosis. We also compared responses to acute inflammatory stimuli in obese and lean mice. Compared with lean control mice, obese mice had baseline decreased lymphatic function. Lymphedema in obese mice further impaired lymphatic function and resulted in increased subcutaneous adipose deposition, increased CD45<sup>+</sup>
and CD4<sup>+</sup>
cell inflammation (<italic>P</italic>
< 0.01), and increased fibrosis, but caused no change in the number of lymphatic vessels. Interestingly, obese mice had a significantly increased acute inflammatory reaction to croton oil application. In conclusion, obese mice have impaired lymphatic function at baseline that is amplified by lymphatic injury. This effect is associated with increased chronic inflammation, fibrosis, and adipose deposition. These findings suggest that obese patients are at higher risk for lymphedema due to impaired baseline lymphatic clearance and an increased propensity for inflammation in response to injury.</p>
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</front>
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