Cell culture models for assessment of GLP-1 receptor agonists application in a translational approach to nonalcoholic fatty liver disease treatment

Author: Martina Smolić, Ana Petrović, Lucija Kuna Roguljić, Tea Omanović Kolarić, Marija Hefer, Dunja Igrec, Karla Rožac, Kristina Bojanić, Vjera Mihaljević, Renata Sikora, Nikola Raguž-Lučić, Tomislav Kizivat, Robert Smolić, George Y. Wu, Aleksandar Včev, Martina Smolić

Faculty: Faculty of Dental Medicine and Health Osijek, J. J. Strossmayer University of Osijek

Country: Croatia

e-mail: msmolic@fdmz.hr

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have been shown to improve glucose and lipid homeostasis, promote weight loss, and reduce cardiovascular risk factors. GLP-1RAs such as liraglutide and semaglutide have been approved for the treatment of T2DM and obesity, but not for non-alcoholic fatty liver disease (NAFLD), despite their promising therapeutic potential. Most recent clinical trials have suggested the importance of early pharmacologic intervention with GLP-1RAs in alleviating and limiting NAFLD, as well as the scarcity of in vitro studies on semaglutide, indicating the need for development of these models. Also, extra-hepatic factors contribute to the GLP-1RA results of in vivo studies. Cell culture models of NAFLD in HepG2 and Huh7 cell lines treated with liraglutide and semaglutide, developed in the Department of Translational Medicine, at Faculty of Dental Medicine and Health Osijek, University of Osijek, provide optimal assessment of their effects directly in liver while eliminating extrahepatic effects on the alleviation of hepatic steatosis, modulation of lipid metabolism pathways, reduction of inflammation, and prevention of the progression of NAFLD to severe hepatic conditions. These models are an important step in bridging the gap between basic and clinical pharmacological research, further investigation of these drugs and their potential implementation beyond obesity and T2DM.