PMID- 38378001
OWN - NLM
STAT- MEDLINE
DCOM- 20240405
LR  - 20240405
IS  - 1932-7420 (Electronic)
IS  - 1550-4131 (Linking)
VI  - 36
IP  - 4
DP  - 2024 Apr 2
TI  - IgG is an aging factor that drives adipose tissue fibrosis and metabolic decline.
PG  - 793-807.e5
LID - S1550-4131(24)00015-9 [pii]
LID - 10.1016/j.cmet.2024.01.015 [doi]
AB  - 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-beta/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.
CI  - Copyright (c) 2024 Elsevier Inc. All rights reserved.
FAU - Yu, Lexiang
AU  - Yu L
AD  - Naomi Berrie Diabetes Center, Department of Medicine, Columbia University, New 
      York, NY 10032, USA.
FAU - Wan, Qianfen
AU  - Wan Q
AD  - Naomi Berrie Diabetes Center, Department of Medicine, Columbia University, New 
      York, NY 10032, USA.
FAU - Liu, Qiongming
AU  - Liu Q
AD  - Naomi Berrie Diabetes Center, Department of Medicine, Columbia University, New 
      York, NY 10032, USA.
FAU - Fan, Yong
AU  - Fan Y
AD  - Naomi Berrie Diabetes Center, Department of Medicine, Columbia University, New 
      York, NY 10032, USA.
FAU - Zhou, Qiuzhong
AU  - Zhou Q
AD  - Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, 
      Singapore, Singapore.
FAU - Skowronski, Alicja A
AU  - Skowronski AA
AD  - Naomi Berrie Diabetes Center, Department of Pediatrics, Columbia University, New 
      York, NY 10032, USA.
FAU - Wang, Summer
AU  - Wang S
AD  - Institute for Cancer Genetics, Department of Pathology and Cell Biology, Columbia 
      University, New York, NY 10032, USA.
FAU - Shao, Zhengping
AU  - Shao Z
AD  - Institute for Cancer Genetics, Department of Pathology and Cell Biology, Columbia 
      University, New York, NY 10032, USA.
FAU - Liao, Chen-Yu
AU  - Liao CY
AD  - Buck Institute for Research on Aging, Novato, CA 94945, USA.
FAU - Ding, Lei
AU  - Ding L
AD  - Department of Rehabilitation and Regenerative Medicine, Department of 
      Microbiology and Immunology, Columbia University Irving Medical Center, New York, 
      NY 10032, USA.
FAU - Kennedy, Brian K
AU  - Kennedy BK
AD  - Buck Institute for Research on Aging, Novato, CA 94945, USA; Healthy Longevity 
      Translational Research Programme, Departments of Biochemistry and Physiology, 
      Yong Loo Lin School of Medicine, National University of Singapore, Centre for 
      Health Longevity, National University Health System, Singapore, Singapore.
FAU - Zha, Shan
AU  - Zha S
AD  - Institute for Cancer Genetics, Department of Pathology and Cell Biology, Columbia 
      University, New York, NY 10032, USA.
FAU - Que, Jianwen
AU  - Que J
AD  - Department of Medicine, Columbia University, New York, NY 10032, USA.
FAU - LeDuc, Charles A
AU  - LeDuc CA
AD  - Naomi Berrie Diabetes Center, Department of Pediatrics, Columbia University, New 
      York, NY 10032, USA.
FAU - Sun, Lei
AU  - Sun L
AD  - Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, 
      Singapore, Singapore.
FAU - Wang, Liheng
AU  - Wang L
AD  - Institute of Cardiovascular Sciences, State Key Laboratory of Vascular 
      Homeostasis and Remodeling, Department of Physiology and Pathophysiology, School 
      of Basic Medical Sciences, Peking University, Beijing 100191, China; Department 
      of Medicine, Division of Endocrinology, Diabetes, Obesity, and Metabolism 
      Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. 
      Electronic address: lihengwang@hsc.pku.edu.cn.
FAU - Qiang, Li
AU  - Qiang L
AD  - Department of Pharmacology, School of Basic Medical Sciences, State Key 
      Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 
      100191, China; Naomi Berrie Diabetes Center, Department of Medicine, Department 
      of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA. 
      Electronic address: qiang@hsc.pku.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20240219
PL  - United States
TA  - Cell Metab
JT  - Cell metabolism
JID - 101233170
RN  - 0 (Immunoglobulin G)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Adipose Tissue
MH  - *Aging/metabolism
MH  - Adipose Tissue, White/metabolism
MH  - Mice, Knockout
MH  - Fibrosis
MH  - Immunoglobulin G
OTO - NOTNLM
OT  - IgG
OT  - adipose tissue
OT  - aging
OT  - fibrosis
OT  - metabolic dysfunction
COIS- Declaration of interests A patent application is pending by Columbia University.
EDAT- 2024/02/21 11:14
MHDA- 2024/04/05 06:43
CRDT- 2024/02/20 18:42
PHST- 2023/05/14 00:00 [received]
PHST- 2023/10/31 00:00 [revised]
PHST- 2024/01/25 00:00 [accepted]
PHST- 2024/04/05 06:43 [medline]
PHST- 2024/02/21 11:14 [pubmed]
PHST- 2024/02/20 18:42 [entrez]
AID - S1550-4131(24)00015-9 [pii]
AID - 10.1016/j.cmet.2024.01.015 [doi]
PST - ppublish
SO  - Cell Metab. 2024 Apr 2;36(4):793-807.e5. doi: 10.1016/j.cmet.2024.01.015. Epub 
      2024 Feb 19.