TM4SF19-mediated control of lysosomal activity in macrophages contributes to obesity-induced inflammation and metabolic dysfunction

Cheoljun Choi, Yujin L. Jeong, Koung-Min Park, Minji Kim, Sangseob Kim, Honghyun Jo, Sumin Lee, Heeseong Kim, Garam Choi, Yoon Ha Choi, Je Kyung Seong, Sik Namgoong, Yeonseok Chung, Young-Suk Jung (), James G. Granneman (), Young-Min Hyun (), Jong Kyoung Kim () and Yun-Hee Lee ()
Additional contact information
Cheoljun Choi: Seoul National University
Yujin L. Jeong: Pohang University of Science and Technology (POSTECH)
Koung-Min Park: Yonsei University College of Medicine
Minji Kim: Seoul National University
Sangseob Kim: Seoul National University
Honghyun Jo: Seoul National University
Sumin Lee: Seoul National University
Heeseong Kim: Seoul National University
Garam Choi: Seoul National University
Yoon Ha Choi: Pohang University of Science and Technology (POSTECH)
Je Kyung Seong: Seoul National University
Sik Namgoong: Korea University College of Medicine
Yeonseok Chung: Seoul National University
Young-Suk Jung: Pusan National University
James G. Granneman: Wayne State University
Young-Min Hyun: Yonsei University College of Medicine
Jong Kyoung Kim: Pohang University of Science and Technology (POSTECH)
Yun-Hee Lee: Seoul National University

Nature Communications, 2024, vol. 15, issue 1, 1-21

Abstract: Abstract Adipose tissue (AT) adapts to overnutrition in a complex process, wherein specialized immune cells remove and replace dysfunctional and stressed adipocytes with new fat cells. Among immune cells recruited to AT, lipid-associated macrophages (LAMs) have emerged as key players in obesity and in diseases involving lipid stress and inflammation. Here, we show that LAMs selectively express transmembrane 4 L six family member 19 (TM4SF19), a lysosomal protein that represses acidification through its interaction with Vacuolar-ATPase. Inactivation of TM4SF19 elevates lysosomal acidification and accelerates the clearance of dying/dead adipocytes in vitro and in vivo. TM4SF19 deletion reduces the LAM accumulation and increases the proportion of restorative macrophages in AT of male mice fed a high-fat diet. Importantly, male mice lacking TM4SF19 adapt to high-fat feeding through adipocyte hyperplasia, rather than hypertrophy. This adaptation significantly improves local and systemic insulin sensitivity, and energy expenditure, offering a potential avenue to combat obesity-related metabolic dysfunction.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-47108-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47108-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-47108-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().