Brown adipose tissue-derived pro-fibrotic protein promotes liver fibrosis
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ABSTRACT: Metabolic dysfunction-associated steatohepatitis (MASH), previously termed non-alcoholic steatohepatitis (NASH), is one of the complications of obesity, known as an extreme form of metabolic dysfunction-associated fatty liver disease (MAFLD). MASH is characterized by fibrosis and sterile liver inflammation that can lead to liver cirrhosis, cancer, and death. The molecular mechanisms of fibrosis in MASH are not fully elucidated, no robust markers for this disease exist, and therapeutic options are still limited. Here we identified a secreted-type pro-fibrotic protein, procollagen C-endopeptidase enhancer-1 (PCPE-1), as one of the brown adipose tissue (BAT)-derived adipokines (BATokines) that promotes liver fibrosis in a murine obese-MASH model. BAT-specific or systemic PCPE-1-knockout models ameliorated liver fibrosis, whereas, PCPE-1 gain of function in BAT enhanced hepatic fibrosis. Our results indicate the suppression of this BATokine may represent a therapeutic modality for MASH.
SUBMITTER: Dr. Ippei Shimizu
PROVIDER: S-SCDT-10_1038-S44318-024-00196-0 | biostudies-other |
REPOSITORIES: biostudies-other
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