ArticleNature metabolism2022
Orosomucoid 2 maintains hepatic lipid homeostasis through suppression of de novo lipogenesis.
Article in Nature metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed.
- Targeting ROAM1 with UDP-GlcNAc nanosheets selective activates lysosomal AMPK to resolve metabolic dysfunction-associated steatotic liver disease.Bioactive materials · 2026Article
- Hepatokine FGL1 drives endothelial injury and atherogenesisActa pharmaceutica Sinica. B · 2026Article
- Microbiotas from extremely preterm infants with growth faltering impair postnatal growth and metabolism in mice.JCI insight · 2026Article
- Hepatokine ORM2 suppresses pathological ferritinophagy to prevent acute tissue injury.Cell death & disease · 2026Article
- Orosomucoid 2 promotes colorectal cancer liver metastasis by suppressing natural killer cell-mediated antitumor immunity by remodeling the serine and one-carbon metabolism pathway.Molecular cancer · 2026Article
- Expanded chromatin accessibility mapping explains genetic variation associated with complex traits in liver.American journal of human genetics · 2026Article
- ORM2 protects against acute pancreatitis by inhibiting premature activation of pancreatic enzymes.Translational gastroenterology and hepatology · 2026Article
- Orosomucoid 2 (ORM2) in type 2 diabetes and coronary artery disease: a potential link between insulin resistance and vascular inflammation.Frontiers in cardiovascular medicine · 2026Review
- Integrated transcriptomics-metabolomics analysis reveals biomarkers and metabolic dysregulation characteristics of parenteral nutrition-associated liver disease.Frontiers in nutrition · 2026Article
- Glial cell crosstalk in Parkinson's disease: Mechanisms, implications, and therapeutic strategies.Fundamental research · 2025Review
- Physiological roles of phosphoinositides and inositol phosphates: Implications for metabolic dysfunction-associated steatotic liver disease.Clinical science (London, England : 1979) · 2025Review
- Inflammation and immunity in liver homeostasis and disease: a nexus of hepatocytes, nonparenchymal cells and immune cells.Cellular & molecular immunology · 2025Review
- Expanded Chromatin Accessibility Mapping Explains Genetic Variation Associated with Complex Traits in Liver.medRxiv : the preprint server for health sciences · 2025Article
- Article
- Secreted proteins in treating metabolic dysfunction-associated steatotic liver disease: from bench towards bedside.Protein & cell · 2025Review
- Bile acid regulation of xenobiotic nuclear receptors on the expressions of orosomucoids in the liver.American journal of physiology. Endocrinology and metabolism · 2025Article
- More than carriers, orosomucoids are key metabolic modulators.Trends in endocrinology and metabolism: TEM · 2025Review
- When getting reactive becomes the nORM: the emerging roles of proinflammatory cholangiokines.Gut · 2025Article
- Association Between Alpha-1-Acid Glycoprotein and Non-Alcoholic Fatty Liver Disease and Liver Fibrosis in Adult Women.Metabolites · 2025Article
- Targeting Histone Deacetylase 11 with a Highly Selective Inhibitor for the Treatment of MASLD.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Non-alcoholic fatty liver disease (NAFLD) is caused by imbalance in lipid metabolism. In this study, we show that the hepatokine orosomucoid (ORM) 2 is a key regulator of de novo lipogenesis in the liver. Hepatic and plasma ORM2 levels are markedly decreased in obese murine models and patients with NAFLD. Through multiple loss- and gain-of function studies, we demonstrate that ORM2 is essential to maintain hepatic and systemic lipid homeostasis. At the mechanistic level, ORM2 binds to inositol 1, 4, 5-trisphosphate receptor type 2 to activate AMP-activated protein kinase signaling, thereby inhibiting sterol regulatory element binding protein 1c-mediated lipogenic gene program. Notably, intraperitoneal injections of recombinant ORM2 protein or stabilized ORM2-FC fusion protein markedly improved liver steatosis, steatohepatitis and atherosclerosis in preclinical mouse models, without adverse effects on body weight or food intake. Thus, these findings suggest that ORM2 may serve as a potential target for therapeutic intervention in NAFLD, non-alcoholic steatohepatitis and related lipid disorders.
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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 Socratic graph.