{
  "abstract": "Transmembrane protein 189 (TMEM189), also known as plasmanylethanolamine desaturase 1 (PEDS1), is involved in plasmalogen biosynthesis, phospholipid metabolism, ferroptosis, and autophagy. However, whether TMEM189/PEDS1 regulates macrophages and disease-related inflammatory responses remains unclear. Here, we for the first time investigated the contribution of TMEM189/PEDS1 to macrophage activation and progression of metabolic dysfunction-associated steatohepatitis (MASH). Experimental data demonstrated that TMEM189 is highly expressed in macrophages, and its inactivation promotes M1 macrophage polarization and increases lipid loading in co-cultured hepatocytes. Loss of Tmem189 in myeloid cells results in a selective increase in the population and activation of monocyte-derived macrophages (MDMs) in the liver, which exacerbates hepatic steatosis, inflammatory damage, and fibrosis in diet-induced MASH mice. The restoration of Tmem189 expression in hepatic macrophages significantly attenuates MASH-related phenotypes. Mechanistically, TMEM189 interacts with fatty acid synthase (FASN), negatively regulates its expression and pro-inflammatory response in macrophages. Further studies revealed that TMEM189 deletion enhances FASN-promoted NLRP3 palmitoylation and its activation, leading to increased IL-1β production, which in turn further accelerates MASH progression. Our findings provide important evidence supporting the critical regulatory role of TMEM189-FASN signaling in liver macrophage activation and MASH progression, which may represent a potential therapeutic target for MASH treatment.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Immunology, School of Basic Medical Sciences Peking University; NHC Key Laboratory of Medical Immunology, Peking University, Beijing, China",
    "Department of General Surgery, Beijing Electric Power Hospital, State Grid Corporation of China; Clinical Medical Research Center for Hepatobiliary Diseases in General Surgery, China General Technology Group, Beijing, China",
    "Medical and Healthy Analytical Center, Peking University, Beijing, China",
    "Center for Human Disease Genomics, Peking University, Beijing, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Pengli Guo"
    },
    {
      "affs": [
        1
      ],
      "name": "Jinqiu Feng"
    },
    {
      "affs": [
        2
      ],
      "name": "Yaxin Lou"
    },
    {
      "affs": [
        0
      ],
      "name": "Tao Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Shufang Ye"
    },
    {
      "affs": [
        0
      ],
      "name": "Yongjun Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Chunlei Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Ping Lv"
    },
    {
      "affs": [
        1
      ],
      "name": "Zongming Zhang"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Yingyu Chen",
      "orcid": "0000-0002-1324-603X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8vtpgbwjjejmt.bib",
  "cited_by": 0,
  "doi": "10.1038/s41419-026-09145-7",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13748651/",
  "id": "8vtpgbwjjejmt",
  "issns": [
    "2041-4889"
  ],
  "landing_url": "https://doi.org/10.1038/s41419-026-09145-7",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2721|Liver Disease Diagnosis and Treatment"
    ]
  ],
  "openalex": "W7202394419",
  "pdf_url": "https://www.nature.com/articles/s41419-026-09145-7_reference.pdf",
  "pmcid": "PMC13748651",
  "pmid": "43003827",
  "published": "2026-08-13",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/8vtpgbwjjejmt.ris",
  "sources": [
    {
      "first_seen": "2026-11-13T12:26:37Z",
      "native_id": "PMC13748651",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s41419-026-09145-7"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2721|Liver Disease Diagnosis and Treatment",
      "subfield": "general"
    }
  ],
  "title": "TMEM189/PEDS1 deficiency aggravates MASH progression by promoting FASN-mediated macrophage activation",
  "title_text": "TMEM189/PEDS1 deficiency aggravates MASH progression by promoting FASN-mediated macrophage activation",
  "type": "peer-reviewed",
  "updated_at": "2026-11-13T12:26:37Z",
  "url": "https://research.draconitic.com/paper/8vtpgbwjjejmt",
  "venue": "Cell Death & Disease",
  "versions": []
}