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Liraglutide downregulates hepatic LDL receptor and PCSK9 expression in HepG2 cells and db/db mice through a HNF-1a dependent mechanism
- Source :
- Cardiovascular Diabetology, Vol 17, Iss 1, Pp 1-10 (2018)
- Publication Year :
- 2018
- Publisher :
- BMC, 2018.
-
Abstract
- Abstract Background Proprotein convertase subtilisin/kexin type 9 (PCSK9), a major regulator of cholesterol homeostasis, is associated with glucose metabolism. Liraglutide, a glucagon-like peptide-1 receptor agonist, can increase insulin secretion in a glucose-dependent manner and lower blood glucose. We aimed to investigate the relationship between liraglutide and PCSK9. Methods At the cellular level, the expressions of PCSK9 and hepatocyte nuclear factor 1 alpha (HNF1α) protein in HepG2 cells stimulated by liraglutide was examined using Western blot. Seven-week old db/db mice and wild type (WT) mice were administered either liraglutide (200 μg/kg) or equivoluminal saline subcutaneously, twice daily for 7 weeks. Fasting glucose level, food intake and body weight were measured every week. After the 7-week treatment, the blood was collected for lipid and PCSK9 levels detection and the liver was removed from the mice for oil red O staining, immunohistochemical analysis, immunofluorescence test and Western bolt. Results Firstly, liraglutide suppressed both PCSK9 and HNF1α expression in HepG2 cells in a time and concentration dependent manner. Secondly, liraglutide induced weight loss in WT and db/db mice, decreased serum PCSK9, glucose and lipid levels and improved hepatic accumulation in db/db but not WT mice. Thirdly, liraglutide reduced both hepatic PCSK9 and low-density lipoprotein receptor (LDLR) expression with a decrease in HNF1α in db/db mice but not in WT mice. Conclusions Liraglutide suppressed PCSK9 expression through HNF1α-dependent mechanism in HepG2 cells and db/db mice, and decreased LDLR possibly via PCSK9-independent pathways in db/db mice.
Details
- Language :
- English
- ISSN :
- 14752840
- Volume :
- 17
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Cardiovascular Diabetology
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.27e55a5e263544838dfa2137262e8512
- Document Type :
- article
- Full Text :
- https://doi.org/10.1186/s12933-018-0689-9