ECE2021 Oral Communications Oral Communications 7: Diabetes, Obesity, Metabolism and Nutrition (6 abstracts)
Liver GPR55 regulates NAFLD progression from steatosis to fibrosis
Uxía Fernández 1 , Marcos Fernández Fondevila 1 , María Jesús González Rellán 1 , NataliaDa Silva Lima 1 , Xabier Buque 2 , Agueda González Rodríguez 3 , Teresa Delgado 4 , Marta Varela Rey 1 , Eva Novoa 1 , MartaTojo 1 , Miguel López 1 , Carlos Diéguez 1 , Miguel Marcos 5 , María Luísa Martínez-Chantar 4 , Marco Arrese 6 , Carmelo García-Monzón 3 , Jose Mato 4 , Patricia Aspichueta 2 & Rubén Nogueiras 1
1CIMUS, University of Santiago de Compostela, Spain; 2 Biocruces Bizkaia Health Research Institute, Spain; 3Instituto de Investigación Sanitaria Princesa, Spain; 4CICBiogune, Spain; 5 University Hospital of Salamanca-Institute of Biomedical Research of Salamanca, Spain; 6Pontificia Universidad Católica de Chile, Chile
Background and aims
G protein-coupled receptor 55 (GPR55) is a putative cannabinoid receptor, and l-α-lysophosphatidylinositol (LPI) is its only known endogenous ligand. Although GPR55 has been linked to energy homeostasis in different organs, its specific role in lipid metabolism in the liver and its contribution to the pathophysiology of non-alcoholic fatty liver disease (NAFLD) remains unknown.
Method
We measured (1) GPR55 expression in the liver of patients with NAFLD compared with individuals without obesity and without liver disease, as well as animal models with steatosis and non-alcoholic steatohepatitis (NASH), and (2) the effects of LPI and genetic disruption of GPR55 in mice, human hepatocytes, and human hepatic stellate cells.
Results
Notably, we found that circulating LPI and liver expression of GPR55 were up-regulated in patients with NASH. LPI induced adenosine monophosphate-activated protein kinase activation of acetyl-coenzyme A carboxylase (ACC) and increased lipid content in human hepatocytes and in the liver of treated mice by inducing de novo lipogenesis and decreasing β-oxidation. The inhibition of GPR55 and ACCα blocked the effects of LPI, and the in vivo knockdown of GPR55 was enough to improve liver damage in mice fed a high-fat diet and in mice fed a methionine-choline-deficient diet. Finally, LPI promoted the initiation of hepatic stellate cell activation by stimulating GPR55 and activation of ACC.
Conclusion
The LPI/GPR55 system plays a role in the development of NAFLD and NASH by activating ACC.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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