title: Deficiency of FcϵR1 Increases Body Weight Gain but Improves Glucose Tolerance in Diet-Induced Obese Mice.
abstract: 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.
authors: Department of Medicine (Y.-J.L., C.L., M.L., G.K.S., K.I., A.S.B., P.L., G.-P.S.), Brigham and Women's Hospital and Harvard Medical School, Department of Genetics and Complex Diseases (K.I.), School of Public Health, Harvard University, and Department of Cell Biology (J.S., R.N.K.), Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts 02115; Department of Cardiology (C.L.), Institute of Clinical Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450003, People's Republic of China; Institute of Cardiology (M.L.), Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430072, People's Republic of China; and NutriOmique team (M.A., S.A., K.C.), Institute of Cardiometabolism and Nutrition, INSERM, Unité Mixte de Recherche en Santé Unité 1166, and NutriOmique team (M.A., S.A., K.C.), Université Pierre et Marie Curie-Paris 6, Paris F-75013 France.
authors: Yun-Jung
authors: YJ
authors: Lee
authors: Department of Medicine (Y.-J.L., C.L., M.L., G.K.S., K.I., A.S.B., P.L., G.-P.S.), Brigham and Women's Hospital and Harvard Medical School, Department of Genetics and Complex Diseases (K.I.), School of Public Health, Harvard University, and Department of Cell Biology (J.S., R.N.K.), Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts 02115; Department of Cardiology (C.L.), Institute of Clinical Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450003, People's Republic of China; Institute of Cardiology (M.L.), Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430072, People's Republic of China; and NutriOmique team (M.A., S.A., K.C.), Institute of Cardiometabolism and Nutrition, INSERM, Unité Mixte de Recherche en Santé Unité 1166, and NutriOmique team (M.A., S.A., K.C.), Université Pierre et Marie Curie-Paris 6, Paris F-75013 France.
authors: Conglin
authors: C
authors: Liu
authors: Department of Medicine (Y.-J.L., C.L., M.L., G.K.S., K.I., A.S.B., P.L., G.-P.S.), Brigham and Women's Hospital and Harvard Medical School, Department of Genetics and Complex Diseases (K.I.), School of Public Health, Harvard University, and Department of Cell Biology (J.S., R.N.K.), Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts 02115; Department of Cardiology (C.L.), Institute of Clinical Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450003, People's Republic of China; Institute of Cardiology (M.L.), Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430072, People's Republic of China; and NutriOmique team (M.A., S.A., K.C.), Institute of Cardiometabolism and Nutrition, INSERM, Unité Mixte de Recherche en Santé Unité 1166, and NutriOmique team (M.A., S.A., K.C.), Université Pierre et Marie Curie-Paris 6, Paris F-75013 France.
authors: Mengyang
authors: M
authors: Liao
authors: Department of Medicine (Y.-J.L., C.L., M.L., G.K.S., K.I., A.S.B., P.L., G.-P.S.), Brigham and Women's Hospital and Harvard Medical School, Department of Genetics and Complex Diseases (K.I.), School of Public Health, Harvard University, and Department of Cell Biology (J.S., R.N.K.), Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts 02115; Department of Cardiology (C.L.), Institute of Clinical Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450003, People's Republic of China; Institute of Cardiology (M.L.), Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430072, People's Republic of China; and NutriOmique team (M.A., S.A., K.C.), Institute of Cardiometabolism and Nutrition, INSERM, Unité Mixte de Recherche en Santé Unité 1166, and NutriOmique team (M.A., S.A., K.C.), Université Pierre et Marie Curie-Paris 6, Paris F-75013 France.
authors: Galina K
authors: GK
authors: Sukhova
authors: Department of Medicine (Y.-J.L., C.L., M.L., G.K.S., K.I., A.S.B., P.L., G.-P.S.), Brigham and Women's Hospital and Harvard Medical School, Department of Genetics and Complex Diseases (K.I.), School of Public Health, Harvard University, and Department of Cell Biology (J.S., R.N.K.), Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts 02115; Department of Cardiology (C.L.), Institute of Clinical Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450003, People's Republic of China; Institute of Cardiology (M.L.), Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430072, People's Republic of China; and NutriOmique team (M.A., S.A., K.C.), Institute of Cardiometabolism and Nutrition, INSERM, Unité Mixte de Recherche en Santé Unité 1166, and NutriOmique team (M.A., S.A., K.C.), Université Pierre et Marie Curie-Paris 6, Paris F-75013 France.
authors: Jun
authors: J
authors: Shirakawa
authors: Department of Medicine (Y.-J.L., C.L., M.L., G.K.S., K.I., A.S.B., P.L., G.-P.S.), Brigham and Women's Hospital and Harvard Medical School, Department of Genetics and Complex Diseases (K.I.), School of Public Health, Harvard University, and Department of Cell Biology (J.S., R.N.K.), Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts 02115; Department of Cardiology (C.L.), Institute of Clinical Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450003, People's Republic of China; Institute of Cardiology (M.L.), Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430072, People's Republic of China; and NutriOmique team (M.A., S.A., K.C.), Institute of Cardiometabolism and Nutrition, INSERM, Unité Mixte de Recherche en Santé Unité 1166, and NutriOmique team (M.A., S.A., K.C.), Université Pierre et Marie Curie-Paris 6, Paris F-75013 France.
authors: Meriem
authors: M
authors: Abdennour
authors: Department of Medicine (Y.-J.L., C.L., M.L., G.K.S., K.I., A.S.B., P.L., G.-P.S.), Brigham and Women's Hospital and Harvard Medical School, Department of Genetics and Complex Diseases (K.I.), School of Public Health, Harvard University, and Department of Cell Biology (J.S., R.N.K.), Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts 02115; Department of Cardiology (C.L.), Institute of Clinical Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450003, People's Republic of China; Institute of Cardiology (M.L.), Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430072, People's Republic of China; and NutriOmique team (M.A., S.A., K.C.), Institute of Cardiometabolism and Nutrition, INSERM, Unité Mixte de Recherche en Santé Unité 1166, and NutriOmique team (M.A., S.A., K.C.), Université Pierre et Marie Curie-Paris 6, Paris F-75013 France.
authors: Karine
authors: K
authors: Iamarene
authors: Department of Medicine (Y.-J.L., C.L., M.L., G.K.S., K.I., A.S.B., P.L., G.-P.S.), Brigham and Women's Hospital and Harvard Medical School, Department of Genetics and Complex Diseases (K.I.), School of Public Health, Harvard University, and Department of Cell Biology (J.S., R.N.K.), Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts 02115; Department of Cardiology (C.L.), Institute of Clinical Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450003, People's Republic of China; Institute of Cardiology (M.L.), Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430072, People's Republic of China; and NutriOmique team (M.A., S.A., K.C.), Institute of Cardiometabolism and Nutrition, INSERM, Unité Mixte de Recherche en Santé Unité 1166, and NutriOmique team (M.A., S.A., K.C.), Université Pierre et Marie Curie-Paris 6, Paris F-75013 France.
authors: Sebastien
authors: S
authors: Andre
authors: Department of Medicine (Y.-J.L., C.L., M.L., G.K.S., K.I., A.S.B., P.L., G.-P.S.), Brigham and Women's Hospital and Harvard Medical School, Department of Genetics and Complex Diseases (K.I.), School of Public Health, Harvard University, and Department of Cell Biology (J.S., R.N.K.), Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts 02115; Department of Cardiology (C.L.), Institute of Clinical Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450003, People's Republic of China; Institute of Cardiology (M.L.), Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430072, People's Republic of China; and NutriOmique team (M.A., S.A., K.C.), Institute of Cardiometabolism and Nutrition, INSERM, Unité Mixte de Recherche en Santé Unité 1166, and NutriOmique team (M.A., S.A., K.C.), Université Pierre et Marie Curie-Paris 6, Paris F-75013 France.
authors: Karen
authors: K
authors: Inouye
authors: Department of Medicine (Y.-J.L., C.L., M.L., G.K.S., K.I., A.S.B., P.L., G.-P.S.), Brigham and Women's Hospital and Harvard Medical School, Department of Genetics and Complex Diseases (K.I.), School of Public Health, Harvard University, and Department of Cell Biology (J.S., R.N.K.), Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts 02115; Department of Cardiology (C.L.), Institute of Clinical Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450003, People's Republic of China; Institute of Cardiology (M.L.), Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430072, People's Republic of China; and NutriOmique team (M.A., S.A., K.C.), Institute of Cardiometabolism and Nutrition, INSERM, Unité Mixte de Recherche en Santé Unité 1166, and NutriOmique team (M.A., S.A., K.C.), Université Pierre et Marie Curie-Paris 6, Paris F-75013 France.
authors: Karine
authors: K
authors: Clement
authors: Department of Medicine (Y.-J.L., C.L., M.L., G.K.S., K.I., A.S.B., P.L., G.-P.S.), Brigham and Women's Hospital and Harvard Medical School, Department of Genetics and Complex Diseases (K.I.), School of Public Health, Harvard University, and Department of Cell Biology (J.S., R.N.K.), Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts 02115; Department of Cardiology (C.L.), Institute of Clinical Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450003, People's Republic of China; Institute of Cardiology (M.L.), Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430072, People's Republic of China; and NutriOmique team (M.A., S.A., K.C.), Institute of Cardiometabolism and Nutrition, INSERM, Unité Mixte de Recherche en Santé Unité 1166, and NutriOmique team (M.A., S.A., K.C.), Université Pierre et Marie Curie-Paris 6, Paris F-75013 France.
authors: Rohit N
authors: RN
authors: Kulkarni
authors: Department of Medicine (Y.-J.L., C.L., M.L., G.K.S., K.I., A.S.B., P.L., G.-P.S.), Brigham and Women's Hospital and Harvard Medical School, Department of Genetics and Complex Diseases (K.I.), School of Public Health, Harvard University, and Department of Cell Biology (J.S., R.N.K.), Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts 02115; Department of Cardiology (C.L.), Institute of Clinical Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450003, People's Republic of China; Institute of Cardiology (M.L.), Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430072, People's Republic of China; and NutriOmique team (M.A., S.A., K.C.), Institute of Cardiometabolism and Nutrition, INSERM, Unité Mixte de Recherche en Santé Unité 1166, and NutriOmique team (M.A., S.A., K.C.), Université Pierre et Marie Curie-Paris 6, Paris F-75013 France.
authors: Alexander S
authors: AS
authors: Banks
authors: Department of Medicine (Y.-J.L., C.L., M.L., G.K.S., K.I., A.S.B., P.L., G.-P.S.), Brigham and Women's Hospital and Harvard Medical School, Department of Genetics and Complex Diseases (K.I.), School of Public Health, Harvard University, and Department of Cell Biology (J.S., R.N.K.), Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts 02115; Department of Cardiology (C.L.), Institute of Clinical Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450003, People's Republic of China; Institute of Cardiology (M.L.), Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430072, People's Republic of China; and NutriOmique team (M.A., S.A., K.C.), Institute of Cardiometabolism and Nutrition, INSERM, Unité Mixte de Recherche en Santé Unité 1166, and NutriOmique team (M.A., S.A., K.C.), Université Pierre et Marie Curie-Paris 6, Paris F-75013 France.
authors: Peter
authors: P
authors: Libby
authors: Department of Medicine (Y.-J.L., C.L., M.L., G.K.S., K.I., A.S.B., P.L., G.-P.S.), Brigham and Women's Hospital and Harvard Medical School, Department of Genetics and Complex Diseases (K.I.), School of Public Health, Harvard University, and Department of Cell Biology (J.S., R.N.K.), Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts 02115; Department of Cardiology (C.L.), Institute of Clinical Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450003, People's Republic of China; Institute of Cardiology (M.L.), Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430072, People's Republic of China; and NutriOmique team (M.A., S.A., K.C.), Institute of Cardiometabolism and Nutrition, INSERM, Unité Mixte de Recherche en Santé Unité 1166, and NutriOmique team (M.A., S.A., K.C.), Université Pierre et Marie Curie-Paris 6, Paris F-75013 France.
authors: Guo-Ping
authors: GP
authors: Shi
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D004734:Energy Metabolism / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D005951:Glucose Tolerance Test; D006801:Humans; D015151:Immunoblotting; D007073:Immunoglobulin E / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D009765:Obesity / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D009767:Obesity, Morbid / Q000097:blood; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D017455:Receptors, IgE / Q000172:deficiency / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015430:Weight Gain / Q000235:genetics*
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; C579617:FcepsilonRIalpha protein, mouse; D047495:PPAR gamma; D017455:Receptors, IgE; D007073:Immunoglobulin E