Deficiency of FcϵR1 Increases Body Weight Gain but Improves Glucose Tolerance in Diet-Induced Obese Mice
| Autor: | Peter Libby, Cong-Lin Liu, Alexander S. Banks, Yun-Jung Lee, Jun Shirakawa, Meriem Abdennour, Karine Clément, Karine Iamarene, Mengyang Liao, Karen Inouye, Galina K. Sukhova, Rohit N. Kulkarni, Sébastien André, Guo-Ping Shi |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Male
medicine.medical_specialty Glucose uptake Immunoblotting Adipose tissue Gene Expression Mice Obese White adipose tissue Diet High-Fat Weight Gain Mice Endocrinology Internal medicine Enhancer binding 3T3-L1 Cells medicine Adipocytes CCAAT-Enhancer-Binding Protein-alpha Animals Humans Obesity Original Research Mice Knockout Glucose tolerance test biology medicine.diagnostic_test Receptors IgE Reverse Transcriptase Polymerase Chain Reaction Glucose Tolerance Test Immunoglobulin E Obesity Morbid Mice Inbred C57BL PPAR gamma Adipose Tissue Adipogenesis biology.protein Female RNA Interference Energy Metabolism Diet-induced obese GLUT4 |
| Zdroj: | Endocrinology. 156(11) |
| ISSN: | 1945-7170 |
| Popis: | Prior studies demonstrated increased plasma IgE in diabetic patients, but the direct participation of IgE in diabetes or obesity remains unknown. This study found that plasma IgE levels correlated inversely with body weight, body mass index, and body fat mass among a population of randomly selected obese women. IgE receptor FcϵR1-deficient (Fcer1a−/−) mice and diet-induced obesity (DIO) mice demonstrated that FcϵR1 deficiency in DIO mice increased food intake, reduced energy expenditure, and increased body weight gain but improved glucose tolerance and glucose-induced insulin secretion. White adipose tissue from Fcer1a−/− mice showed an increased expression of phospho-AKT, CCAAT/enhancer binding protein-α, peroxisome proliferator-activated receptor-γ, glucose transporter-4 (Glut4), and B-cell lymphoma 2 (Bcl2) but reduced uncoupling protein 1 (UCP1) and phosphorylated c-Jun N-terminal kinase (JNK) expression, tissue macrophage accumulation, and apoptosis, suggesting that IgE reduces adipogenesis and glucose uptake but induces energy expenditure, adipocyte apoptosis, and white adipose tissue inflammation. In 3T3-L1 cells, IgE inhibited the expression of CCAAT/enhancer binding protein-α and peroxisome proliferator-activated receptor-γ, and preadipocyte adipogenesis and induced adipocyte apoptosis. IgE reduced the 3T3-L1 cell expression of Glut4, phospho-AKT, and glucose uptake, which concurred with improved glucose tolerance in Fcer1a−/− mice. This study established two novel pathways of IgE in reducing body weight gain in DIO mice by suppressing adipogenesis and inducing adipocyte apoptosis while worsening glucose tolerance by reducing Glut4 expression, glucose uptake, and insulin secretion. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|