Loss of OcaB prevents age-induced fat accretion and insulin resistance by altering B-lymphocyte transition and promoting energy expenditure

Sophie Carter, Stéphanie Miard, Alexandre Caron, Sandrine Sallé-Lefort, Philippe St-Pierre, Fernando Forato Anhê, Emilie Lavoie-Charland, Pascale Blais-Lecours, Marie Claude Drolet, Julie S. Lefebvre, Julie Lacombe, Yves Deshaies, Jacques Couet, Mathieu Laplante, Mathieu Ferron, Yohan Bossé, André Marette, Denis Richard, David Marsolais, Frédéric Picard

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

The current demographic shift toward an aging population has led to a robust increase in the prevalence of age-associated metabolic disorders. Recent studies have demonstrated that the etiology of obesity-related insulin resistance that develops with aging differs from that induced by high-calorie diets. Whereas the role of adaptive immunity in changes in energy metabolism driven by nutritional challenges has recently gained attention, its impact on aging remains mostly unknown. Here we found that the number of follicular B2 lymphocytes and expression 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 IgG and impaired glucose homeostasis. Reduction of B-cell maturation and Ig 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 2 / 2 mice replenished the 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.

Original languageEnglish (US)
Pages (from-to)1285-1296
Number of pages12
JournalDiabetes
Volume67
Issue number7
DOIs
StatePublished - Jul 2018
Externally publishedYes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Carter, S., Miard, S., Caron, A., Sallé-Lefort, S., St-Pierre, P., Anhê, F. F., Lavoie-Charland, E., Blais-Lecours, P., Drolet, M. C., Lefebvre, J. S., Lacombe, J., Deshaies, Y., Couet, J., Laplante, M., Ferron, M., Bossé, Y., Marette, A., Richard, D., Marsolais, D., & Picard, F. (2018). Loss of OcaB prevents age-induced fat accretion and insulin resistance by altering B-lymphocyte transition and promoting energy expenditure. Diabetes, 67(7), 1285-1296. https://doi.org/10.2337/db17-0558