PRMT3 inhibitor SGC707 reduces triglyceride levels and induces pruritus in Western-type diet-fed LDL receptor knockout mice
| Autor: | de Jong, Laura M, Zhang, Zhengzheng, den Hartog, Yvette, Sijsenaar, Timothy J P, Martins Cardoso, Renata, Manson, Martijn L, Hankemeier, Thomas, Lindenburg, Peter W, Salvatori, Daniela C F, Van Eck, Miranda, Hoekstra, Menno, Anatomie en fysiologie, CS_Locomotion, CS_Cancer |
|---|---|
| Přispěvatelé: | Anatomie en fysiologie, CS_Locomotion, CS_Cancer |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Male
Protein-Arginine N-Methyltransferases LDL/deficiency Science Knockout Inbred C57BL Receptors LDL/deficiency Article Fatty Liver/drug therapy Receptors G-Protein-Coupled Diet Western/adverse effects Mice Liver/drug effects Receptors Animals Humans Protein-Arginine N-Methyltransferases/antagonists & inhibitors General Triglycerides G-Protein-Coupled/genetics Mice Knockout Western/adverse effects Isoquinolines/adverse effects Multidisciplinary Pruritus Isoquinolines Lipids Diet Fatty Liver Mice Inbred C57BL Triglycerides/blood Metabolism Pruritus/etiology Liver Receptors LDL Diet Western Medicine Receptors G-Protein-Coupled/genetics |
| Zdroj: | Scientific Reports, 12(1) Scientific Reports, 12(1), 1. NLM (Medline) Scientific Reports, Vol 12, Iss 1, Pp 1-12 (2022) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Protein arginine methyltransferase 3 (PRMT3) is a co-activator of liver X receptor capable of selectively modulating hepatic triglyceride synthesis. Here we investigated whether pharmacological PRMT3 inhibition can diminish the hepatic steatosis extent and lower plasma lipid levels and atherosclerosis susceptibility. Hereto, male hyperlipidemic low-density lipoprotein receptor knockout mice were fed an atherogenic Western-type diet and injected 3 times per week intraperitoneally with PRMT3 inhibitor SGC707 or solvent control. Three weeks into the study, SGC707-treated mice developed severe pruritus and scratching-associated skin lesions, leading to early study termination. SGC707-treated mice exhibited 50% lower liver triglyceride stores as well as 32% lower plasma triglyceride levels. Atherosclerotic lesions were virtually absent in all experimental mice. Plasma metabolite analysis revealed that levels of taurine-conjugated bile acids were ~ threefold increased (P |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink