Gavin Fredrickson, Kira Florczak, Fanta Barrow, Shamsed Mahmud, Katrina Dietsche, Haiguang Wang, Preethy Parthiban, Andrew Hakeem, Rawan Almutlaq, Oyedele Adeyi, Adam Herman, Alessandro Bartolomucci, Christopher Staley, Xiao Dong, Cyrus Jahansouz, Jesse W. Williams, Douglas G. Mashek, Sayeed Ikramuddin, Xavier S. Revelo
{"title":"TREM2 macrophages mediate the beneficial effects of bariatric surgery against MASH","authors":"Gavin Fredrickson, Kira Florczak, Fanta Barrow, Shamsed Mahmud, Katrina Dietsche, Haiguang Wang, Preethy Parthiban, Andrew Hakeem, Rawan Almutlaq, Oyedele Adeyi, Adam Herman, Alessandro Bartolomucci, Christopher Staley, Xiao Dong, Cyrus Jahansouz, Jesse W. Williams, Douglas G. Mashek, Sayeed Ikramuddin, Xavier S. Revelo","doi":"10.1097/hep.0000000000001098","DOIUrl":null,"url":null,"abstract":"For patients with obesity and metabolic syndrome, bariatric procedures such as vertical sleeve gastrectomy (VSG) have a clear benefit in ameliorating metabolic dysfunction-associated steatohepatitis (MASH). While the effects of bariatric surgeries have been mainly attributed to nutrient restriction and malabsorption, whether immuno-modulatory mechanisms are involved remains unclear. Using murine models, we report that VSG ameliorates MASH progression in a weight loss-independent manner. Single-cell RNA sequencing revealed that hepatic lipid-associated macrophages (LAMs) expressing the triggering receptor expressed on myeloid cells 2 (TREM2) repress inflammation and increase their lysosomal activity in response to VSG. Remarkably, TREM2 deficiency in mice ablates the reparative effects of VSG, suggesting that TREM2 is required for MASH resolution. Mechanistically, TREM2 prevents the inflammatory activation of macrophages and is required for their efferocytic function. Overall, our findings indicate that bariatric surgery improves MASH through a reparative process driven by TREM2<jats:sup>+</jats:sup> macrophages, providing insights into the mechanisms of disease reversal that may result in new therapies and improved surgical interventions.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":null,"pages":null},"PeriodicalIF":12.9000,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hepatology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/hep.0000000000001098","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
For patients with obesity and metabolic syndrome, bariatric procedures such as vertical sleeve gastrectomy (VSG) have a clear benefit in ameliorating metabolic dysfunction-associated steatohepatitis (MASH). While the effects of bariatric surgeries have been mainly attributed to nutrient restriction and malabsorption, whether immuno-modulatory mechanisms are involved remains unclear. Using murine models, we report that VSG ameliorates MASH progression in a weight loss-independent manner. Single-cell RNA sequencing revealed that hepatic lipid-associated macrophages (LAMs) expressing the triggering receptor expressed on myeloid cells 2 (TREM2) repress inflammation and increase their lysosomal activity in response to VSG. Remarkably, TREM2 deficiency in mice ablates the reparative effects of VSG, suggesting that TREM2 is required for MASH resolution. Mechanistically, TREM2 prevents the inflammatory activation of macrophages and is required for their efferocytic function. Overall, our findings indicate that bariatric surgery improves MASH through a reparative process driven by TREM2+ macrophages, providing insights into the mechanisms of disease reversal that may result in new therapies and improved surgical interventions.
期刊介绍:
HEPATOLOGY is recognized as the leading publication in the field of liver disease. It features original, peer-reviewed articles covering various aspects of liver structure, function, and disease. The journal's distinguished Editorial Board carefully selects the best articles each month, focusing on topics including immunology, chronic hepatitis, viral hepatitis, cirrhosis, genetic and metabolic liver diseases, liver cancer, and drug metabolism.