최철준 (서울대학교 약학대학)

한빛사논문

조회383

최철준Cheoljun Choi

서울대학교 약학대학

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Nat. Commun., Mar 30 2024, 15 (1) | https://doi.org/10.1038/s41467-024-47108-8 TM4SF19-mediated control of lysosomal activity in macrophages contributes to obesity-induced inflammation and metabolic dysfunction

Cheoljun Choi ^1,8, Yujin L. Jeong ^2,8, Koung-Min Park ^3,8, Minji Kim ¹, Sangseob Kim ¹, Honghyun Jo ¹, Sumin Lee ¹, Heeseong Kim ¹, Garam Choi ¹, Yoon Ha Choi ², Je Kyung Seong⁴, Sik Namgoong ⁵, Yeonseok Chung ¹, Young-Suk Jung⁶ , James G. Granneman ⁷, Young-Min Hyun ³ , Jong Kyoung Kim ² & Yun-Hee Lee ¹

¹College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea.

²Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang 37673, Republic of Korea.

³Department of Anatomy and Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.

⁴Korea Mouse Phenotyping Center (KMPC), and Laboratory of Developmental Biology and Genomics, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.

⁵Department of Plastic Surgery, Korea University College of Medicine, Seoul, Republic of Korea.

⁶Department of Pharmacy, College of Pharmacy, Research Institute for Drug Development, Pusan National University, Busan, Republic of Korea.

⁷Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, USA.

⁸These authors contributed equally: Cheoljun Choi, Yujin L. Jeong, Koung-Min Park.

Corresponding authors

Correspondence to Young-Suk Jung, James G. Granneman, Young-Min Hyun, Jong Kyoung Kim or Yun-Hee Lee.

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.

논문정보

형식Research article
게재일2024년 03월 (BRIC 등록일 2024-04-01)
연구진국내(교신)+국외 연구진
분야 의약학 > 약학

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