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- W4220846945 abstract "Abstract Non-alcoholic steatohepatitis (NASH) and type 2 diabetes are closely linked, yet the pathophysiological mechanisms underpinning this bidirectional relationship remain unresolved. Using proteomic approaches, we interrogate hepatocyte protein secretion in two models of murine NASH to understand how liver-derived factors modulate lipid metabolism and insulin sensitivity in peripheral tissues. We reveal striking hepatokine remodelling that is associated with insulin resistance and maladaptive lipid metabolism, and identify arylsulfatase A (ARSA) as a hepatokine that is upregulated in NASH and type 2 diabetes. Mechanistically, hepatic ARSA reduces sulfatide content and increases lysophosphatidylcholine (LPC) accumulation within lipid rafts and suppresses LPC secretion from the liver, thereby lowering circulating LPC and lysophosphatidic acid (LPA) levels. Reduced LPA is linked to improvements in skeletal muscle insulin sensitivity and systemic glycemic control. Hepatic silencing of Arsa or inactivation of ARSA’s enzymatic activity reverses these effects. Together, this study provides a unique resource describing global changes in hepatokine secretion in NASH, and identifies ARSA as a regulator of liver to muscle communication and as a potential therapeutic target for type 2 diabetes." @default.
- W4220846945 created "2022-04-03" @default.
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- W4220846945 date "2022-03-10" @default.
- W4220846945 modified "2023-10-15" @default.
- W4220846945 title "Deep proteomic profiling unveils arylsulfatase A as a non-alcoholic steatohepatitis inducible hepatokine and regulator of glycemic control" @default.
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- W4220846945 doi "https://doi.org/10.1038/s41467-022-28889-2" @default.
- W4220846945 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35273160" @default.
- W4220846945 hasPublicationYear "2022" @default.
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