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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MDPI AG
2020-07-01
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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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institution | Directory Open Access Journal |
issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-10T18:20:22Z |
publishDate | 2020-07-01 |
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series | International Journal of Molecular Sciences |
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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