Loss of OcaB Prevents Age-Induced Fat Accretion and Insulin Resistance by Altering B-Lymphocyte Transition and Promoting Energy Expenditure
| Autor: | Jacques Couet, Mathieu Laplante, Stéphanie Miard, Yohan Bossé, Pascale Blais-Lecours, Julie Lacombe, Frédéric Picard, Denis Richard, Julie S. Lefebvre, Marie Claude Drolet, Philippe St-Pierre, Sandrine Sallé-Lefort, Mathieu Ferron, Sophie Carter, Emilie Lavoie-Charland, Fernando F. Anhê, Alexandre Caron, Yves Deshaies, André Marette, David Marsolais |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Adult
Male 0301 basic medicine Aging medicine.medical_specialty Adolescent Endocrinology Diabetes and Metabolism Lymphocyte Population White adipose tissue Immunoglobulin G Mice Young Adult 03 medical and health sciences Insulin resistance Internal medicine Glucose Intolerance Brown adipose tissue Internal Medicine medicine Animals Humans Glucose homeostasis Obesity education Cells Cultured Aged Epididymis Mice Knockout B-Lymphocytes education.field_of_study biology Cell Differentiation Middle Aged Lipid Metabolism Acquired immune system medicine.disease Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Endocrinology Trans-Activators biology.protein Female Insulin Resistance Energy Metabolism |
| Zdroj: | Diabetes. 67:1285-1296 |
| ISSN: | 1939-327X 0012-1797 |
| Popis: | The current demographic shift toward an aging population has led to a robust increase in the prevalence of age-associated metabolic disorders. Interestingly, recent studies have demonstrated that the etiology of obesity-related insulin resistance developed upon aging differs from that induced by high-calorie diets. Whereas the role of adaptive immunity on the changes in energy metabolism driven by nutritional challenges has gained attention in the past years, its impact upon aging remains mostly unknown. Here, we found that follicular B2 lymphocytes and expression levels of the B cell-specific transcriptional coactivator OcaB increase with age in spleen and in intra-abdominal epididymal white adipose tissue (eWAT), concomitantly with higher circulating levels of immunoglobulin G (IgG) and impaired glucose homeostasis. Reduction of B cell maturation and immunoglobulin production - especially that of IgG2c - by ablation of OcaB prevented age-induced glucose intolerance and insulin resistance, and promoted energy expenditure by stimulating fatty acid utilization in eWAT and brown adipose tissue. Transfer of wild-type bone marrow in OcaB-/- mice replenished eWAT B2 cell population and IgG levels, which diminished glucose tolerance, insulin sensitivity, and energy expenditure, while increasing body weight gain in aged mice. Thus, these findings demonstrate that upon aging, modifications in B cell-driven adaptive immunity contribute to glucose intolerance and fat accretion. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|