ArticleThe Journal of clinical investigation2021
TREM2 sustains macrophage-hepatocyte metabolic coordination in nonalcoholic fatty liver disease and sepsis.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 157 papers.
What it found
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Who cites it
157 citing papers in PubMed, 221 citations in OpenAlex.
- Targeted inhibition of inflammatory liver macrophages with a multifunctional nanoparticle ameliorates metabolic dysfunction-associated steatohepatitis.Bioactive materials · 2027Article
- Multi-omic analysis of jaw-bone periosteum identifies the role of macrophage-derived SPP1 in CtskBone research · 2026Article
- Extracellular Vesicle Surface Protein Profiling in Metabolic Dysfunction-associated Steatotic Liver Disease in Obesity.Journal of extracellular biology · 2026Article
- Gene-Based Clustering Identifies QSOX1 and IL1RAP as Biomarkers of Metabolic Dysfunction-Associated Steatotic Liver Disease.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- Article
- Liver Macrophages in the Pathogenesis of Viral Hepatitis.Current issues in molecular biology · 2026Review
- Soluble TREM2 engages cell-surface nucleolin to drive vascular permeability and malignant ascites in ovarian cancer.EMBO molecular medicine · 2026Article
- Meta-inflammation through the lens of macrophage programming and nutrient-sensing ghrelin signaling.Immunometabolism (Cobham, Surrey) · 2026Review
- Macrophage metabolism reprogramming in sepsis: Pathogenesis and therapeutic implications (Review).International journal of molecular medicine · 2026Review
- Article
- TREM2 sustains glucose metabolic homeostasis to drive antibacterial defense during sepsis.iScience · 2026Article
- The relationship between urinary tract infections and sepsis: results from Mendelian randomization and MIMIC data study.World journal of urology · 2026Article
- Synthetic cleavage-resistant TREM2 boosts macrophage efferocytosis to treat inflammatory diseases.Cell reports. Medicine · 2026Article
- TGFBI promotes liver fibrosis through remodeling the profibrotic microenvironment by a positive feedback regulatory loop.Communications biology · 2026Article
- Obesity-induced pyroptotic adipocyte death leads to TREM2-dependent macrophage dysfunction and adipose tissue inflammation.iScience · 2026Article
- The Role of Kupffer Cells and Liver Macrophages in the Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease.Biomedicines · 2026Review
- Harnessing the microbiome to regulate myeloid TREM2 expression and innate immune responses.ImmunoHorizons · 2026Article
- TREM2-expressing macrophages in liver diseases.Trends in endocrinology and metabolism: TEM · 2026Review
- The TREM2 paradox in fibrosis: a unified mechanism for opposite outcomes across organs.Frontiers in immunology · 2026Review
- Gut barrier-microbiota crosstalk in sepsis: from pathogenesis to potential therapies.Frontiers in immunology · 2026Review
97 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 9 institutions in 2 countries.
Funding
Abstract
Sepsis is a leading cause of death in critical illness, and its pathophysiology varies depending on preexisting medical conditions. Here we identified nonalcoholic fatty liver disease (NAFLD) as an independent risk factor for sepsis in a large clinical cohort and showed a link between mortality in NAFLD-associated sepsis and hepatic mitochondrial and energetic metabolism dysfunction. Using in vivo and in vitro models of liver lipid overload, we discovered a metabolic coordination between hepatocyte mitochondria and liver macrophages that express triggering receptor expressed on myeloid cells-2 (TREM2). Trem2-deficient macrophages released exosomes that impaired hepatocytic mitochondrial structure and energy supply because of their high content of miR-106b-5p, which blocks Mitofusin 2 (Mfn2). In a mouse model of NAFLD-associated sepsis, TREM2 deficiency accelerated the initial progression of NAFLD and subsequent susceptibility to sepsis. Conversely, overexpression of TREM2 in liver macrophages improved hepatic energy supply and sepsis outcome. This study demonstrates that NAFLD is a risk factor for sepsis, providing a basis for precision treatment, and identifies hepatocyte-macrophage metabolic coordination and TREM2 as potential targets for future clinical trials.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.