TY - JOUR
T1 - Loss of OcaB prevents age-induced fat accretion and insulin resistance by altering B-lymphocyte transition and promoting energy expenditure
AU - Carter, Sophie
AU - Miard, Stéphanie
AU - Caron, Alexandre
AU - Sallé-Lefort, Sandrine
AU - St-Pierre, Philippe
AU - Anhê, Fernando Forato
AU - Lavoie-Charland, Emilie
AU - Blais-Lecours, Pascale
AU - Drolet, Marie Claude
AU - Lefebvre, Julie S.
AU - Lacombe, Julie
AU - Deshaies, Yves
AU - Couet, Jacques
AU - Laplante, Mathieu
AU - Ferron, Mathieu
AU - Bossé, Yohan
AU - Marette, André
AU - Richard, Denis
AU - Marsolais, David
AU - Picard, Frédéric
N1 - Publisher Copyright:
© 2018 by the American Diabetes Association.
PY - 2018/7
Y1 - 2018/7
N2 - 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.
AB - 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.
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U2 - 10.2337/db17-0558
DO - 10.2337/db17-0558
M3 - Article
C2 - 29496744
AN - SCOPUS:85051610780
SN - 0012-1797
VL - 67
SP - 1285
EP - 1296
JO - Diabetes
JF - Diabetes
IS - 7
ER -