IgG is an aging factor that drives adipose tissue fibrosis and metabolic decline
Copyright © 2024 Elsevier Inc. All rights reserved..
Aging is underpinned by pronounced metabolic decline; however, the drivers remain obscure. Here, we report that IgG accumulates during aging, particularly in white adipose tissue (WAT), to impair adipose tissue function and metabolic health. Caloric restriction (CR) decreases IgG accumulation in WAT, whereas replenishing IgG counteracts CR's metabolic benefits. IgG activates macrophages via Ras signaling and consequently induces fibrosis in WAT through the TGF-β/SMAD pathway. Consistently, B cell null mice are protected from aging-associated WAT fibrosis, inflammation, and insulin resistance, unless exposed to IgG. Conditional ablation of the IgG recycling receptor, neonatal Fc receptor (FcRn), in macrophages prevents IgG accumulation in aging, resulting in prolonged healthspan and lifespan. Further, targeting FcRn by antisense oligonucleotide restores WAT integrity and metabolic health in aged mice. These findings pinpoint IgG as a hidden culprit in aging and enlighten a novel strategy to rejuvenate metabolic health.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:36 |
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| Enthalten in: |
Cell metabolism - 36(2024), 4 vom: 02. Apr., Seite 793-807.e5 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yu, Lexiang [VerfasserIn] |
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| Links: |
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| Themen: |
Adipose tissue |
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| Anmerkungen: |
Date Completed 05.04.2024 Date Revised 05.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.cmet.2024.01.015 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 520 | |a Aging is underpinned by pronounced metabolic decline; however, the drivers remain obscure. Here, we report that IgG accumulates during aging, particularly in white adipose tissue (WAT), to impair adipose tissue function and metabolic health. Caloric restriction (CR) decreases IgG accumulation in WAT, whereas replenishing IgG counteracts CR's metabolic benefits. IgG activates macrophages via Ras signaling and consequently induces fibrosis in WAT through the TGF-β/SMAD pathway. Consistently, B cell null mice are protected from aging-associated WAT fibrosis, inflammation, and insulin resistance, unless exposed to IgG. Conditional ablation of the IgG recycling receptor, neonatal Fc receptor (FcRn), in macrophages prevents IgG accumulation in aging, resulting in prolonged healthspan and lifespan. Further, targeting FcRn by antisense oligonucleotide restores WAT integrity and metabolic health in aged mice. These findings pinpoint IgG as a hidden culprit in aging and enlighten a novel strategy to rejuvenate metabolic health | ||
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| 700 | 1 | |a Wan, Qianfen |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Qiongming |e verfasserin |4 aut | |
| 700 | 1 | |a Fan, Yong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Qiuzhong |e verfasserin |4 aut | |
| 700 | 1 | |a Skowronski, Alicja A |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Summer |e verfasserin |4 aut | |
| 700 | 1 | |a Shao, Zhengping |e verfasserin |4 aut | |
| 700 | 1 | |a Liao, Chen-Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Ding, Lei |e verfasserin |4 aut | |
| 700 | 1 | |a Kennedy, Brian K |e verfasserin |4 aut | |
| 700 | 1 | |a Zha, Shan |e verfasserin |4 aut | |
| 700 | 1 | |a Que, Jianwen |e verfasserin |4 aut | |
| 700 | 1 | |a LeDuc, Charles A |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Lei |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Liheng |e verfasserin |4 aut | |
| 700 | 1 | |a Qiang, Li |e verfasserin |4 aut | |
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