O-1602 Promotes Hepatic Steatosis through GPR55 and PI3 Kinase/Akt/SREBP-1c Signaling in Mice

Autor: Saeromi Kang, Ae-Yeon Lee, Soyoung Park, Dong-Soon Im, Kwang-Hyeon Liu
Rok vydání: 2021
Předmět:
0301 basic medicine
Intracellular Space
Chronic liver disease
Benzoates
lysophosphatidylinositol
lcsh:Chemistry
chemistry.chemical_compound
Liver disease
Mice
Phosphatidylinositol 3-Kinases
0302 clinical medicine
Non-alcoholic Fatty Liver Disease
steatosis
Cannabidiol
Receptor
Receptors
Cannabinoid
lcsh:QH301-705.5
Spectroscopy
Kinase
Fatty liver
General Medicine
Hep G2 Cells
Lipids
Computer Science Applications
Liver
Lysophosphatidylinositol
hepatocytes
Sterol Regulatory Element Binding Protein 1
Signal Transduction
medicine.medical_specialty
Diet
High-Fat
Models
Biological
Catalysis
Article
Inorganic Chemistry
03 medical and health sciences
Internal medicine
medicine
Animals
Humans
Physical and Theoretical Chemistry
Molecular Biology
Protein kinase B
Triglycerides
Organic Chemistry
medicine.disease
030104 developmental biology
Endocrinology
chemistry
lcsh:Biology (General)
lcsh:QD1-999
Calcium
Steatosis
Lysophospholipids
GPR55
Azabicyclo Compounds
Proto-Oncogene Proteins c-akt
030217 neurology & neurosurgery
Zdroj: International Journal of Molecular Sciences
International Journal of Molecular Sciences, Vol 22, Iss 3091, p 3091 (2021)
Volume 22
Issue 6
ISSN: 1422-0067
Popis: Non-alcoholic fatty liver disease is recognized as the leading cause of chronic liver disease. Overnutrition and obesity are associated with hepatic steatosis. G protein-coupled receptor 55 (GPR55) has not been extensively studied in hepatic steatosis, although its endogenous ligands have been implicated in liver disease progression. Therefore, the functions of GPR55 were investigated in Hep3B human hepatoma cells and mice fed high-fat diets. O-1602, the most potent agonist of GPR55, induced lipid accumulation in hepatocytes, which was reversed by treatment with CID16020046, an antagonist of GPR55. O-1602 also induced intracellular calcium rise in Hep3B cells in a GPR55-independent manner. O-1602-induced lipid accumulation was dependent on the PI3 kinase/Akt/SREBP-1c signaling cascade. Furthermore, we found increased levels of lysophosphatidylinositol species of 16:0, 18:0, 18:1, 18:2, 20:1, and 20:2 in the livers of mice fed a high-fat diet for 4 weeks. One-week treatment with CID16020046 suppressed high-fat diet-induced lipid accumulation and O-1602-induced increase of serum triglyceride levels in vivo. Therefore, the present data suggest the pro-steatotic function of GPR55 signaling in hepatocytes and provide a potential therapeutic target for non-alcoholic fatty liver disease.
Databáze: OpenAIRE
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