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The Role of GLP1-RAs in Direct Modulation of Lipid Metabolism in Hepatic Tissue as Determined Using In Vitro Models
Ana Petrovic1,2, Dunja Igrec1, Karla Rozac1
1Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia.
Abstract:
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. They are a promising therapeutic option for non-alcoholic fatty liver disease (NAFLD), the most common liver disease, associated with T2DM, obesity, and metabolic syndrome. GLP-1RAs have been approved for the treatment of T2DM and obesity, but not for NAFLD. Most recent clinical trials have suggested the importance of early pharmacologic intervention with GLP-1RAs in alleviating and limiting NAFLD, as well as highlighting the relative scarcity of in vitro studies on semaglutide, indicating the need for further research. However, extra-hepatic factors contribute to the GLP-1RA results of in vivo studies. Cell culture models of NAFLD can be helpful in 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. In this review article, we discuss the role of GLP-1 and GLP-1RA in the treatment of NAFLD using human hepatocyte models.
Insights
Glucagon-like peptide 1 receptor agonists show promise for treating non-alcoholic fatty liver disease (NAFLD). Human hepatocyte models are crucial for understanding their effects, free from external influences.
Area of Science:
- Hepatology
- Endocrinology
- Pharmacology
Background:
- Non-alcoholic fatty liver disease (NAFLD) is a prevalent liver condition linked to type 2 diabetes (T2DM), obesity, and metabolic syndrome.
- Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are approved for T2DM and obesity, demonstrating benefits in glucose/lipid control, weight loss, and cardiovascular health.
- While promising for NAFLD, GLP-1RAs are not yet approved for this indication, and in vivo study results can be confounded by extra-hepatic factors.
Purpose of the Study:
- To review the role of GLP-1 and GLP-1RAs in managing NAFLD.
- To emphasize the utility of human hepatocyte models for investigating GLP-1RA efficacy in NAFLD.
- To highlight the need for further in vitro research, particularly on semaglutide.
Main Methods:
- Review of existing literature on GLP-1 and GLP-1RAs in the context of NAFLD.
- Focus on studies utilizing human hepatocyte cell culture models.
- Analysis of how these models help isolate hepatic effects.
Main Results:
- GLP-1RAs demonstrate potential in alleviating hepatic steatosis and modulating lipid metabolism pathways in NAFLD.
- In vitro models facilitate the assessment of GLP-1RA effects on inflammation and disease progression, independent of extra-hepatic influences.
- Evidence suggests early intervention with GLP-1RAs may limit NAFLD severity.
Conclusions:
- Human hepatocyte models provide a valuable tool to elucidate the direct effects of GLP-1RAs on NAFLD pathogenesis.
- Further in vitro research is essential to fully understand the therapeutic potential of GLP-1RAs, including semaglutide, for NAFLD treatment.
- GLP-1RAs represent a promising therapeutic avenue for NAFLD, warranting continued investigation in controlled cellular environments.
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