ArticleNature communications2022
Deep proteomic profiling unveils arylsulfatase A as a non-alcoholic steatohepatitis inducible hepatokine and regulator of glycemic control.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Endurance exercise elicits a hepatic memory associated with improved metabolic function and protein secretion.Molecular metabolism · 2026Article
- OAF Blocks SIAH1-Mediated Degradation of SCPX, a Therapeutic Strategy for MASLD.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- HFpEF and MASLD: converging mechanisms and clinical implications.Nature reviews. Cardiology · 2026Review
- Timed secreted proteomes reveal regulation of hepatokines by the liver circadian clock.Nature communications · 2026Article
- Early elevation of complement-related proteins in metabolic dysfunction-associated steatotic liver disease (MASLD) with normal liver enzymes.BMC gastroenterology · 2025Article
- HEXA-FC protein therapy increases skeletal muscle glucose uptake and improves glycaemic control in mice with insulin resistance and in a mouse model of type 2 diabetes.Diabetologia · 2025Article
- Decoding the Liver-Heart Axis in Cardiometabolic Diseases.Circulation research · 2025Review
- Integrated liver-secreted and plasma proteomics identify a predictive model that stratifies MASH.Cell reports. Medicine · 2025Article
- Sulfation pathways in the maintenance of functional beta-cell mass and implications for diabetes.Essays in biochemistry · 2024Review
- Single-base tiled screen unveils design principles of PspCas13b for potent and off-target-free RNA silencing.Nature structural & molecular biology · 2024Article
- Targeting hepatic ceruloplasmin mitigates nonalcoholic steatohepatitis by modulating bile acid metabolism.Journal of molecular cell biology · 2024Article
- Drug targets regulate systemic metabolism and provide new horizons to treat nonalcoholic steatohepatitis.Metabolism open · 2024Review
- Liver-derived extracellular vesicles improve whole-body glycaemic control via inter-organ communication.Nature metabolism · 2024Article
- Relationship of Sulfatides Physiological Function and Peroxisome Proliferator-Activated Receptor α.Neurochemical research · 2023Review
- Environmental exposures are important risk factors for advanced liver fibrosis in African American adults.JHEP reports : innovation in hepatology · 2023Article
- Article
- Proteomic analysis reveals exercise training induced remodelling of hepatokine secretion and uncovers syndecan-4 as a regulator of hepatic lipid metabolism.Molecular metabolism · 2022Article
- Liver Protein Expression in NASH Mice on a High-Fat Diet: Response to Multi-Mineral Intervention.Frontiers in nutrition · 2022Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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