황성환 (부산대학교, NIH) | 한빛사논문 > 한빛사

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조회297

황성환Seonghwan Hwang

부산대학교, NIH

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J. Clin. Invest., Nov 03 2025, 135 (21) e190635 | https://doi.org/10.1172/JCI190635 Adipocyte death promotes hepatic infiltration of S100A8+ macrophages and steatotic liver disease progression in mice

Yukun Guan,¹ Yeonsoo Kim,² Yang Wang,¹ Ye Eun Cho,² Xiaogang Xiang,¹ Seung-Jin Kim,¹ Tiantian Yao,¹ Dechun Feng,¹ Seonghwan Hwang,^1,2 and Bin Gao¹

¹Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism (NIAAA), NIH, Bethesda, Maryland, USA.
²College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan, South Korea.

YG and YK contributed equally to this work and are co–first authors.
SH and BG are the co–senior authors.
Address correspondence to: Seonghwan Hwang or Bin Gao

Abstract

Both adipocytes and hepatocytes have the capacity to store fat, but the factor(s) that determine fat distribution between these cell types remain unknown. In mice fed a high-fat diet, fat initially accumulates predominantly in adipocytes, while hepatic fat accumulation mainly emerges after the onset of epididymal adipocyte death that results in elevated free fatty acids to promote lipid accumulation in hepatocytes. However, it remains unclear whether other signals after adipocyte death are required to direct and/or promote hepatocytes to store fat and subsequently trigger metabolic dysfunction-associated steatotic liver disease (MASLD, formerly known as nonalcoholic fatty liver disease). Using genetically modified mouse models combined with bulk and single-cell RNA-Seq analysis, we demonstrated that visceral adipocyte death induced an accumulation of S100A8+ macrophages in the liver, which was partially induced by fatty acids and apoptotic adipocyte-derived extracellular vesicles. Macrophage-specific deletion of the S100a8 gene reduced hepatic fat accumulation and MASLD severity in mice. Mechanistically, S100A8+ macrophages suppressed cellular communication network factor 3 (CCN3), a negative regulator of CD36, thereby enhancing CD36 expression in hepatocytes. In conclusion, adipocyte death promotes hepatic infiltration of S100A8+ macrophages, which drive hepatocyte lipid storage and subsequently promote MASLD progression through CD36 upregulation, partially mediated by CCN3 suppression.

논문정보

형식Research article
게재일2025년 11월 (BRIC 등록일 2025-11-04)
연구진국내(교신)+국외 연구진
분야 의약학 > 약리의학

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