B-Cell-Activating Factor Depletion Ameliorates Aging-Dependent Insulin Resistance via Enhancement of Thermogenesis in Adipose Tissues

Impaired glucose tolerance is a common feature associated with human aging, which is caused by defects in insulin secretion, insulin action or both. Recent studies have suggested that B-cell-activating factor (BAFF), a cytokine that modulates proliferation and differentiation of B cells, and its rec...

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Main Authors: Bobae Kim, Chang-Kee Hyun
Format: Article
Language:English
Published: MDPI AG 2020-07-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/21/14/5121
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author Bobae Kim
Chang-Kee Hyun
author_facet Bobae Kim
Chang-Kee Hyun
author_sort Bobae Kim
collection DOAJ
description Impaired glucose tolerance is a common feature associated with human aging, which is caused by defects in insulin secretion, insulin action or both. Recent studies have suggested that B-cell-activating factor (BAFF), a cytokine that modulates proliferation and differentiation of B cells, and its receptors are expressed in mature adipocytes and preadipocytes, proposing BAFF as a potential regulator of energy metabolism. In this study, we show that systemic BAFF depletion improves aging-dependent insulin resistance. In aged (10-month-old) BAFF<sup>−/−</sup> mice, glucose tolerance and insulin sensitivity were significantly improved despite higher adiposity as a result of expansion of adipose tissues compared to wild-type controls. BAFF<sup>−/−</sup> mice displayed an improved response to acute cold challenge, commensurate with the up-regulated expression of thermogenic genes in both brown and subcutaneous adipose tissues. These changes were found to be mediated by both increased M2-like (alternative) macrophage activation and enhanced leptin and FGF21 production, which may account for the improving effect of BAFF depletion on insulin resistance. In addition, leptin-deficient mice (ob/ob) showed augmented BAFF signaling concomitant with impaired thermogenic activity, identifying BAFF as a suppressive factor to thermogenesis. Our findings suggest that suppression of BAFF could be a therapeutic approach to attenuate aging-dependent insulin resistance.
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spelling doaj.art-f303ff5eabc94bd8979d4b7508cf93b92023-11-20T07:22:46ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-07-012114512110.3390/ijms21145121B-Cell-Activating Factor Depletion Ameliorates Aging-Dependent Insulin Resistance via Enhancement of Thermogenesis in Adipose TissuesBobae Kim0Chang-Kee Hyun1School of Life Science, Handong Global University, Pohang, Gyungbuk 37554, KoreaSchool of Life Science, Handong Global University, Pohang, Gyungbuk 37554, KoreaImpaired glucose tolerance is a common feature associated with human aging, which is caused by defects in insulin secretion, insulin action or both. Recent studies have suggested that B-cell-activating factor (BAFF), a cytokine that modulates proliferation and differentiation of B cells, and its receptors are expressed in mature adipocytes and preadipocytes, proposing BAFF as a potential regulator of energy metabolism. In this study, we show that systemic BAFF depletion improves aging-dependent insulin resistance. In aged (10-month-old) BAFF<sup>−/−</sup> mice, glucose tolerance and insulin sensitivity were significantly improved despite higher adiposity as a result of expansion of adipose tissues compared to wild-type controls. BAFF<sup>−/−</sup> mice displayed an improved response to acute cold challenge, commensurate with the up-regulated expression of thermogenic genes in both brown and subcutaneous adipose tissues. These changes were found to be mediated by both increased M2-like (alternative) macrophage activation and enhanced leptin and FGF21 production, which may account for the improving effect of BAFF depletion on insulin resistance. In addition, leptin-deficient mice (ob/ob) showed augmented BAFF signaling concomitant with impaired thermogenic activity, identifying BAFF as a suppressive factor to thermogenesis. Our findings suggest that suppression of BAFF could be a therapeutic approach to attenuate aging-dependent insulin resistance.https://www.mdpi.com/1422-0067/21/14/5121B-cell-activating factor (BAFF)aging-dependent insulin resistancenon-shivering thermogenesisbrown adipose tissueadipose tissue browning
spellingShingle Bobae Kim
Chang-Kee Hyun
B-Cell-Activating Factor Depletion Ameliorates Aging-Dependent Insulin Resistance via Enhancement of Thermogenesis in Adipose Tissues
International Journal of Molecular Sciences
B-cell-activating factor (BAFF)
aging-dependent insulin resistance
non-shivering thermogenesis
brown adipose tissue
adipose tissue browning
title B-Cell-Activating Factor Depletion Ameliorates Aging-Dependent Insulin Resistance via Enhancement of Thermogenesis in Adipose Tissues
title_full B-Cell-Activating Factor Depletion Ameliorates Aging-Dependent Insulin Resistance via Enhancement of Thermogenesis in Adipose Tissues
title_fullStr B-Cell-Activating Factor Depletion Ameliorates Aging-Dependent Insulin Resistance via Enhancement of Thermogenesis in Adipose Tissues
title_full_unstemmed B-Cell-Activating Factor Depletion Ameliorates Aging-Dependent Insulin Resistance via Enhancement of Thermogenesis in Adipose Tissues
title_short B-Cell-Activating Factor Depletion Ameliorates Aging-Dependent Insulin Resistance via Enhancement of Thermogenesis in Adipose Tissues
title_sort b cell activating factor depletion ameliorates aging dependent insulin resistance via enhancement of thermogenesis in adipose tissues
topic B-cell-activating factor (BAFF)
aging-dependent insulin resistance
non-shivering thermogenesis
brown adipose tissue
adipose tissue browning
url https://www.mdpi.com/1422-0067/21/14/5121
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AT changkeehyun bcellactivatingfactordepletionamelioratesagingdependentinsulinresistanceviaenhancementofthermogenesisinadiposetissues