Multiomics analyses decipher intricate changes in the cellular and metabolic landscape of steatotic livers upon dietary restriction and sleeve gastrectomy.

IF 8.2 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
International Journal of Biological Sciences Pub Date : 2024-08-19 eCollection Date: 2024-01-01 DOI:10.7150/ijbs.98362
Shuai Chen, Qinghe Zeng, Xiurong Cai, Jiaming Xue, Guo Yin, Peng Song, Liming Tang, Christophe Klein, Frank Tacke, Adrien Guillot, Hanyang Liu
{"title":"Multiomics analyses decipher intricate changes in the cellular and metabolic landscape of steatotic livers upon dietary restriction and sleeve gastrectomy.","authors":"Shuai Chen, Qinghe Zeng, Xiurong Cai, Jiaming Xue, Guo Yin, Peng Song, Liming Tang, Christophe Klein, Frank Tacke, Adrien Guillot, Hanyang Liu","doi":"10.7150/ijbs.98362","DOIUrl":null,"url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic, progressive liver disease that encompasses a spectrum of steatosis, steatohepatitis (or MASH), and fibrosis. Evidence suggests that dietary restriction (DR) and sleeve gastrectomy (SG) can lead to remission of hepatic steatosis and inflammation through weight loss, but it is unclear whether these procedures induce distinct metabolic or immunological changes in MASLD livers. This study aims to elucidate the intricate hepatic changes following DR, SG or sham surgery in rats fed a high-fat diet as a model of obesity-related MASLD, in comparison to a clinical cohort of patients undergoing SG. Single-cell and single-nuclei transcriptome analysis, spatial metabolomics, and immunohistochemistry revealed the liver landscape, while circulating biomarkers were measured in serum samples. Artificial intelligence (AI)-assisted image analysis characterized the spatial distribution of hepatocytes, myeloid cells and lymphocytes. In patients and experimental MASLD rats, SG improved body mass index, circulating liver injury biomarkers and triglyceride levels. Both DR and SG attenuated liver steatosis and fibrosis in rats. Metabolism-related genes (<i>Ppara</i>, <i>Cyp2e1</i> and <i>Cyp7a1</i>) were upregulated in hepatocytes upon DR and SG, while SG broadly upregulated lipid metabolism on cholangiocytes, monocytes, macrophages, and neutrophils. Furthermore, SG promoted restorative myeloid cell accumulation in the liver not only ameliorating inflammation but activating liver repair processes. Regions with potent myeloid infiltration were marked with enhanced metabolic capacities upon SG. Additionally, a disruption of periportal hepatocyte functions was observed upon DR. In conclusion, this study indicates a dynamic cellular crosstalk in steatotic livers of patients undergoing SG. Notably, PPARα- and gut-liver axis-related processes, and metabolically active myeloid cell infiltration indicate intervention-related mechanisms supporting the indication of SG for the treatment of MASLD.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"20 11","pages":"4438-4457"},"PeriodicalIF":8.2000,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11380448/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Biological Sciences","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.7150/ijbs.98362","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic, progressive liver disease that encompasses a spectrum of steatosis, steatohepatitis (or MASH), and fibrosis. Evidence suggests that dietary restriction (DR) and sleeve gastrectomy (SG) can lead to remission of hepatic steatosis and inflammation through weight loss, but it is unclear whether these procedures induce distinct metabolic or immunological changes in MASLD livers. This study aims to elucidate the intricate hepatic changes following DR, SG or sham surgery in rats fed a high-fat diet as a model of obesity-related MASLD, in comparison to a clinical cohort of patients undergoing SG. Single-cell and single-nuclei transcriptome analysis, spatial metabolomics, and immunohistochemistry revealed the liver landscape, while circulating biomarkers were measured in serum samples. Artificial intelligence (AI)-assisted image analysis characterized the spatial distribution of hepatocytes, myeloid cells and lymphocytes. In patients and experimental MASLD rats, SG improved body mass index, circulating liver injury biomarkers and triglyceride levels. Both DR and SG attenuated liver steatosis and fibrosis in rats. Metabolism-related genes (Ppara, Cyp2e1 and Cyp7a1) were upregulated in hepatocytes upon DR and SG, while SG broadly upregulated lipid metabolism on cholangiocytes, monocytes, macrophages, and neutrophils. Furthermore, SG promoted restorative myeloid cell accumulation in the liver not only ameliorating inflammation but activating liver repair processes. Regions with potent myeloid infiltration were marked with enhanced metabolic capacities upon SG. Additionally, a disruption of periportal hepatocyte functions was observed upon DR. In conclusion, this study indicates a dynamic cellular crosstalk in steatotic livers of patients undergoing SG. Notably, PPARα- and gut-liver axis-related processes, and metabolically active myeloid cell infiltration indicate intervention-related mechanisms supporting the indication of SG for the treatment of MASLD.

多组学分析解密了脂肪肝患者在饮食限制和袖带状胃切除术后细胞和代谢情况的复杂变化。
代谢功能障碍相关性脂肪性肝病(MASLD)是一种慢性进展性肝病,包括脂肪变性、脂肪性肝炎(或 MASH)和纤维化。有证据表明,饮食限制(DR)和袖状胃切除术(SG)可通过减轻体重来缓解肝脏脂肪变性和炎症,但目前还不清楚这些手术是否会诱导 MASLD 肝脏发生不同的代谢或免疫学变化。本研究旨在通过与接受 SG 手术的临床患者进行比较,阐明以高脂肪饮食喂养的大鼠作为肥胖相关 MASLD 模型,在接受 DR、SG 或假手术后肝脏发生的复杂变化。单细胞和单核转录组分析、空间代谢组学和免疫组化揭示了肝脏的结构,同时对血清样本中的循环生物标记物进行了测量。人工智能(AI)辅助图像分析描述了肝细胞、骨髓细胞和淋巴细胞的空间分布。在患者和实验性 MASLD 大鼠中,SG 可改善体重指数、循环肝损伤生物标志物和甘油三酯水平。DR和SG都能减轻大鼠肝脏脂肪变性和纤维化。DR和SG可上调肝细胞中的代谢相关基因(Ppara、Cyp2e1和Cyp7a1),而SG可广泛上调胆管细胞、单核细胞、巨噬细胞和中性粒细胞的脂质代谢。此外,SG 还能促进肝脏中恢复性髓系细胞的聚集,不仅能改善炎症,还能激活肝脏修复过程。髓系细胞强力浸润的区域在 SG 作用下代谢能力明显增强。此外,DR 会破坏肝脏周围肝细胞的功能。总之,这项研究表明,接受 SG 治疗的脂肪肝患者体内存在动态的细胞串联。值得注意的是,PPARα和肠肝轴相关过程以及代谢活跃的髓样细胞浸润表明了干预相关机制,支持将 SG 用于治疗 MASLD。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
International Journal of Biological Sciences
International Journal of Biological Sciences 生物-生化与分子生物学
CiteScore
16.90
自引率
1.10%
发文量
413
审稿时长
1 months
期刊介绍: The International Journal of Biological Sciences is a peer-reviewed, open-access scientific journal published by Ivyspring International Publisher. It dedicates itself to publishing original articles, reviews, and short research communications across all domains of biological sciences.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信