Arteriosclerosis, thrombosis, and vascular biology, 2011-10, Vol.31 (10), p.2251-2260
2011
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Details
- Autor(en) / Beteiligte
- Titel
- CD40L deficiency ameliorates adipose tissue inflammation and metabolic manifestations of obesity in mice
- Ist Teil von
- Arteriosclerosis, thrombosis, and vascular biology, 2011-10, Vol.31 (10), p.2251-2260
- Ort / Verlag
- United States
- Erscheinungsjahr
- 2011
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Obese adipose tissue shows hallmarks of chronic inflammation, which promotes the development of metabolic disorders. The mechanisms by which immune cells interact with each other or with metabolism-associated cell types, and the players involved, are still unclear. The CD40-CD40L costimulatory dyad plays a pivotal role in immune responses and in diseases such as atherosclerosis and may therefore be a mediator of obesity. Here we investigated whether CD40L is involved in adipose tissue inflammation and its associated metabolic changes. To assess a putative role of CD40L in obesity in vivo, we evaluated metabolic and inflammatory consequences of 18 weeks of high-fat feeding in CD40L(+/+) and CD40L(-/-) mice. In addition, C57Bl6 mice were injected with neutralizing anti-CD40L (αCD40L) antibody for 12 weeks while being fed a high-fat diet. Genetic deficiency of CD40L attenuated the development of diet-induced obesity, hepatic steatosis, and increased systemic insulin sensitivity. In adipose tissue, it impaired obesity-induced immune cell infiltration and the associated deterioration of glucose and lipid metabolism. Accordingly, αCD40L treatment improved systemic insulin sensitivity, glucose tolerance, and CD4(+) T-cell infiltration in adipose tissue with limited effects on adipose tissue weight. CD40L plays a crucial role in the development of obesity-induced inflammation and metabolic complications.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1079-5642eISSN: 1524-4636DOI: 10.1161/atvbaha.111.231357Titel-ID: cdi_pubmed_primary_21817098
- Format
- –
- Schlagworte
- Adipose Tissue - immunology, Adipose Tissue - metabolism, Animals, Antibodies, Neutralizing - administration & dosage, Blood Glucose - metabolism, CD4-Positive T-Lymphocytes - immunology, CD40 Ligand - deficiency, CD40 Ligand - genetics, CD40 Ligand - immunology, Disease Models, Animal, Fatty Liver - genetics, Fatty Liver - immunology, Fatty Liver - metabolism, Fatty Liver - prevention & control, Inflammation Mediators - metabolism, Insulin - blood, Insulin Resistance, Lipid Metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Obesity - complications, Obesity - genetics, Obesity - immunology, Obesity - metabolism, Obesity - physiopathology, Obesity - prevention & control, Panniculitis - genetics, Panniculitis - immunology, Panniculitis - metabolism, Panniculitis - prevention & control, Time Factors, Weight Gain